Variant rs367327 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000153.4(GALC):c.1620A>G(p.Thr540=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,609,970 control chromosomes in the GnomAD database, including 791,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70143 hom., cov: 31)

Exomes 𝑓: 0.99 ( 720877 hom. )

Consequence

GALC
NM_000153.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.81

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-87945603-T-C is Benign according to our data. Variant chr14-87945603-T-C is described in ClinVar as [Benign]. Clinvar id is 167118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87945603-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.81 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.1620A>G	p.Thr540=	synonymous_variant	14/17	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.1620A>G	p.Thr540=	synonymous_variant	14/17	1	NM_000153.4	ENSP00000261304	P1	P54803-1

Frequencies

GnomAD3 genomes

AF:

0.959

AC:

145664

AN:

151938

Hom.:

70104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

0.938

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.964

GnomAD3 exomes

AF:

0.985

AC:

245232

AN:

248934

Hom.:

120938

AF XY:

0.988

AC XY:

133465

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.863

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

0.939

Gnomad SAS exome

AF:

0.997

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.994

AC:

1449420

AN:

1457914

Hom.:

720877

Cov.:

AF XY:

0.995

AC XY:

721779

AN XY:

725526

show subpopulations

Gnomad4 AFR exome

AF:

0.859

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.998

Gnomad4 EAS exome

AF:

0.953

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.986

GnomAD4 genome

AF:

0.959

AC:

145763

AN:

152056

Hom.:

70143

Cov.:

AF XY:

0.960

AC XY:

71334

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.984

Gnomad4 ASJ

AF:

0.998

Gnomad4 EAS

AF:

0.938

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.965

Alfa

AF:

0.989

Hom.:

82896

Bravo

AF:

0.952

Asia WGS

AF:

0.961

AC:

3342

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 27, 2015	- -
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	-	- -

Galactosylceramide beta-galactosidase deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 16, 2019	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.36

DANN

Benign

0.30

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