dbSNP rs12432149: GALC:c.1671-15C>T (chr14-87941573-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000153.4(GALC):c.1671-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,498,288 control chromosomes in the GnomAD database, including 210,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17740 hom., cov: 32)

Exomes 𝑓: 0.53 ( 192280 hom. )

Consequence

GALC
NM_000153.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.03

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=-0.9).

BP6

Variant 14-87941573-G-A is Benign according to our data. Variant chr14-87941573-G-A is described in ClinVar as [Benign]. Clinvar id is 92496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87941573-G-A is described in Lovd as [Benign].

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 rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.1671-15C>T		intron_variant	Intron 14 of 16	ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 link	c.1671-15C>T		intron_variant	Intron 14 of 16	1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69840

AN:

151698

Hom.:

17739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.551

AC:

136630

AN:

248100

Hom.:

39307

AF XY:

0.552

AC XY:

74351

AN XY:

134636

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.513

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.529

AC:

712053

AN:

1346472

Hom.:

192280

Cov.:

AF XY:

0.531

AC XY:

358949

AN XY:

676576

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.757

Gnomad4 SAS exome

AF:

0.579

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.520

Gnomad4 OTH exome

AF:

0.528

GnomAD4 genome

AF:

0.460

AC:

69846

AN:

151816

Hom.:

17740

Cov.:

AF XY:

0.466

AC XY:

34566

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.521

Gnomad4 OTH

AF:

0.468

Alfa

AF:

0.492

Hom.:

3781

Bravo

AF:

0.456

Asia WGS

AF:

0.560

AC:

1948

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 03, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Galactosylceramide beta-galactosidase deficiency

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.024

DANN

Benign

0.26

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