chr14-87950751-GA-G

Variant names:

• chr14-87950751-GA-G
• rs11300320
• NM_000153.4:c.1162-4delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000153.4(GALC):​c.1162-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (69014 hom., cov: 0)
  • Exomes 𝑓: 0.97 (530192 hom.)
• Consequence: GALC NM_000153.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:17
• Conservation: PhyloP100: -0.150
• Publications: 7 publications found

Genes affected

GALC (HGNC:4115): (galactosylceramidase) This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

GALC Gene-Disease associations (from GenCC):

• Krabbe disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-87950751-GA-G is Benign according to our data. Variant chr14-87950751-GA-G is described in ClinVar as Benign. ClinVar VariationId is 92493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000153.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	NM_000153.4	MANE Select	c.1162-4delT		splice_region intron	N/A	NP_000144.2
	GALC	NM_001201401.2		c.1093-4delT		splice_region intron	N/A	NP_001188330.1
	GALC	NM_001201402.2		c.1084-4delT		splice_region intron	N/A	NP_001188331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	ENST00000261304.7	TSL:1 MANE Select	c.1162-4delT		splice_region intron	N/A	ENSP00000261304.2
	GALC	ENST00000393568.8	TSL:2	c.1093-4delT		splice_region intron	N/A	ENSP00000377198.4
	GALC	ENST00000393569.6	TSL:2	c.1084-4delT		splice_region intron	N/A	ENSP00000377199.2

Frequencies

GnomAD3 genomes AF: 0.959 AC: 143279 AN: 149400 Hom.: 68984 Cov.: 0

Gnomad AFR AF: 0.859

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.966

GnomAD2 exomes AF: 0.974 AC: 207143 AN: 212618 AF XY: 0.977

Gnomad AFR exome AF: 0.841

Gnomad AMR exome AF: 0.972

Gnomad ASJ exome AF: 0.985

Gnomad EAS exome AF: 0.983

Gnomad FIN exome AF: 0.994

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.975

GnomAD4 exome AF: 0.967 AC: 1097368 AN: 1134968 Hom.: 530192 Cov.: 0 AF XY: 0.969 AC XY: 554172 AN XY: 572076

African (AFR) AF: 0.818 AC: 22461 AN: 27468

American (AMR) AF: 0.967 AC: 37240 AN: 38492

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 21237 AN: 21760

East Asian (EAS) AF: 0.980 AC: 33322 AN: 34012

South Asian (SAS) AF: 0.972 AC: 68299 AN: 70232

European-Finnish (FIN) AF: 0.986 AC: 47063 AN: 47746

Middle Eastern (MID) AF: 0.975 AC: 4700 AN: 4820

European-Non Finnish (NFE) AF: 0.970 AC: 817173 AN: 842760

Other (OTH) AF: 0.962 AC: 45873 AN: 47678

GnomAD4 genome AF: 0.959 AC: 143367 AN: 149512 Hom.: 69014 Cov.: 0 AF XY: 0.961 AC XY: 69986 AN XY: 72826

African (AFR) AF: 0.858 AC: 34971 AN: 40738

American (AMR) AF: 0.985 AC: 14686 AN: 14914

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3453 AN: 3460

East Asian (EAS) AF: 1.00 AC: 5073 AN: 5074

South Asian (SAS) AF: 0.999 AC: 4731 AN: 4734

European-Finnish (FIN) AF: 0.999 AC: 10007 AN: 10018

Middle Eastern (MID) AF: 0.997 AC: 289 AN: 290

European-Non Finnish (NFE) AF: 0.999 AC: 67239 AN: 67296

Other (OTH) AF: 0.966 AC: 2008 AN: 2078

Alfa AF: 0.953 Hom.: 6173

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:17

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Aug 01, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Galactosylceramide beta-galactosidase deficiency Benign:6

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

May 12, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

European Non-Finnish population allele frequency is 97.92% (rs751373579, 109,537/111,048 alleles, 54,014 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:4

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

May 16, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The GALC c.1162-4delT variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a polymorphism outcome for this variant. This variant was found in 104106/106498 control chromosomes (50900 homozygotes) at a frequency of 0.9775395, which is approximately 437 times the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361), suggesting this variant is likely a benign polymorphism and the major allele in general population. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign.

Apr 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Abnormal brain morphology Pathogenic:1

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Likely pathogenic

Review Status: flagged submission

Collection Method: research

GALC-related disorder Benign:1

Jun 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15
Mutation Taster		=98/2	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11300320; hg19: chr14-88417095; COSMIC: COSV54323120; COSMIC: COSV54323120;