Variant rs17687109 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000622264.4(GALC):c.1187T>C(p.Leu396Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,595,282 control chromosomes in the GnomAD database, including 17,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1141 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16067 hom. )

Consequence

GALC
ENST00000622264.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0150

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 14-87963346-A-G is Benign according to our data. Variant chr14-87963346-A-G is described in ClinVar as [Benign]. Clinvar id is 255369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.1161+38T>C		intron_variant		ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 link	c.1161+38T>C		intron_variant		1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17183

AN:

152032

Hom.:

1138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0953

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.126

AC:

31394

AN:

248394

Hom.:

2334

AF XY:

0.126

AC XY:

16980

AN XY:

134750

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.00201

Gnomad SAS exome

AF:

0.0988

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.143

AC:

207088

AN:

1443132

Hom.:

16067

Cov.:

AF XY:

0.142

AC XY:

102468

AN XY:

719364

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.00164

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.113

AC:

17192

AN:

152150

Hom.:

1141

Cov.:

AF XY:

0.113

AC XY:

8434

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0951

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.144

Hom.:

2314

Bravo

AF:

0.107

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Galactosylceramide beta-galactosidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.64

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

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