rs398076

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000153.4(GALC):c.1350C>T(p.Ser450Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,610,008 control chromosomes in the GnomAD database, including 126,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12159 hom., cov: 31)

Exomes 𝑓: 0.39 ( 113955 hom. )

Consequence

GALC
NM_000153.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.109

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-87947867-G-A is Benign according to our data. Variant chr14-87947867-G-A is described in ClinVar as [Benign]. Clinvar id is 92494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87947867-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.109 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.1350C>T	p.Ser450Ser	synonymous_variant	Exon 13 of 17	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.1350C>T	p.Ser450Ser	synonymous_variant	Exon 13 of 17	1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60115

AN:

151636

Hom.:

12146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.395

GnomAD2 exomes

AF:

0.368

AC:

91227

AN:

248096

AF XY:

0.372

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.392

AC:

571804

AN:

1458254

Hom.:

113955

Cov.:

AF XY:

0.393

AC XY:

284890

AN XY:

725544

show subpopulations

African (AFR)

AF:

0.435

AC:

14494

AN:

33322

American (AMR)

AF:

0.281

AC:

12518

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10793

AN:

26064

East Asian (EAS)

AF:

0.194

AC:

7686

AN:

39630

South Asian (SAS)

AF:

0.385

AC:

33156

AN:

86202

European-Finnish (FIN)

AF:

0.399

AC:

21312

AN:

53358

Middle Eastern (MID)

AF:

0.383

AC:

2204

AN:

5752

European-Non Finnish (NFE)

AF:

0.402

AC:

446430

AN:

1109190

Other (OTH)

AF:

0.386

AC:

23211

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

16362

32724

49086

65448

81810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.396

AC:

60162

AN:

151754

Hom.:

12159

Cov.:

AF XY:

0.394

AC XY:

29204

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.431

AC:

17830

AN:

41346

American (AMR)

AF:

0.340

AC:

5172

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1469

AN:

3468

East Asian (EAS)

AF:

0.186

AC:

953

AN:

5128

South Asian (SAS)

AF:

0.392

AC:

1889

AN:

4818

European-Finnish (FIN)

AF:

0.412

AC:

4352

AN:

10562

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27133

AN:

67884

Other (OTH)

AF:

0.401

AC:

846

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1818

3636

5454

7272

9090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.395

Hom.:

37166

Bravo

AF:

0.390

Asia WGS

AF:

0.369

AC:

1283

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.384

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

Oct 27, 2015

Eurofins Ntd Llc (ga)

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

(source)

DANN

Benign

0.61

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs398076

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over