Variant chr14-87986637-C-T 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 NM_000153.4(GALC):c.329-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,314,266 control chromosomes in the GnomAD database, including 13,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1139 hom., cov: 31)

Exomes 𝑓: 0.14 ( 12723 hom. )

Consequence

GALC
NM_000153.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.131

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-87986637-C-T is Benign according to our data. Variant chr14-87986637-C-T is described in ClinVar as [Benign]. Clinvar id is 255375.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	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.329-35G>A		intron_variant		ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.329-35G>A		intron_variant		1	NM_000153.4	P1	P54803-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17102

AN:

151750

Hom.:

1136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.0954

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.127

AC:

30189

AN:

237698

Hom.:

2155

AF XY:

0.127

AC XY:

16291

AN XY:

128668

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.00247

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.142

AC:

164569

AN:

1162398

Hom.:

12723

Cov.:

AF XY:

0.140

AC XY:

83213

AN XY:

592304

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.00170

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.113

AC:

17111

AN:

151868

Hom.:

1139

Cov.:

AF XY:

0.113

AC XY:

8377

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00233

Gnomad4 SAS

AF:

0.0953

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.136

Hom.:

307

Bravo

AF:

0.107

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.65

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