14-87933543-TATC-T

Position:

• chr14-87933543-TATC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000153.4(GALC):​c.*1186_*1188delGAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 155,638 control chromosomes in the GnomAD database, including 18,478 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17813 hom., cov: 0)
  • Exomes 𝑓: 0.58 (665 hom.)
• Consequence: GALC NM_000153.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-87933543-TATC-T is Benign according to our data. Variant chr14-87933543-TATC-T is described in ClinVar as [Benign]. Clinvar id is 314732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4	c.*1186_*1188delGAT		3_prime_UTR_variant	17/17	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304	c.*1186_*1188delGAT		3_prime_UTR_variant	17/17	1	NM_000153.4	ENSP00000261304.2
GALC	ENST00000555000.5	n.*74+353_*74+355delGAT		intron_variant		2		ENSP00000450472.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70340 AN: 151632 Hom.: 17809 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.575 AC: 2237 AN: 3888 Hom.: 665 AF XY: 0.578 AC XY: 1154 AN XY: 1998

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.464 AC: 70357 AN: 151750 Hom.: 17813 Cov.: 0 AF XY: 0.469 AC XY: 34796 AN XY: 74146

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.472

Alfa AF: 0.495 Hom.: 2409

Bravo AF: 0.461

Asia WGS AF: 0.561 AC: 1942 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs141199615; hg19: chr14-88399887; COSMIC: COSV54323828; COSMIC: COSV54323828;