Variant 14-87950751-GAA-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000153.4(GALC):c.1162-4del variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:15

Conservation

PhyloP100: -0.150

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 92493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87950751-GA-G is described in Lovd as [Pathogenic]. Variant chr14-87950751-GA-G is described in Lovd as [Benign]. Variant chr14-87950751-GA-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.1162-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.1162-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000153.4	P1	P54803-1

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

143279

AN:

149400

Hom.:

68984

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.974

AC:

207143

AN:

212618

Hom.:

100902

AF XY:

0.977

AC XY:

112939

AN XY:

115542

show subpopulations

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 SAS exome

AF:

0.984

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.:

AF XY:

0.969

AC XY:

554172

AN XY:

572076

show subpopulations

Gnomad4 AFR exome

AF:

0.818

Gnomad4 AMR exome

AF:

0.967

Gnomad4 ASJ exome

AF:

0.976

Gnomad4 EAS exome

AF:

0.980

Gnomad4 SAS exome

AF:

0.972

Gnomad4 FIN exome

AF:

0.986

Gnomad4 NFE exome

AF:

0.970

Gnomad4 OTH exome

AF:

0.962

GnomAD4 genome

AF:

0.959

AC:

143367

AN:

149512

Hom.:

69014

Cov.:

AF XY:

0.961

AC XY:

69986

AN XY:

72826

show subpopulations

Gnomad4 AFR

AF:

0.858

Gnomad4 AMR

AF:

0.985

Gnomad4 ASJ

AF:

0.998

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.966

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 01, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Galactosylceramide beta-galactosidase deficiency

Benign:5

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	May 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Genetics, Royal Melbourne Hospital	May 04, 2023	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 -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 16, 2016	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. -

Abnormal brain morphology

Pathogenic:1

Likely pathogenic, flagged submission

research

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

- -

GALC-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

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 v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over