rs112992946

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.42G>C(p.Ala14Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,586,138 control chromosomes in the GnomAD database, including 16,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A14A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1114 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15584 hom. )

Consequence

GALC
NM_000153.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0380

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

Krabbe disease
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp

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=-0.74).

BP6

Variant 14-87993123-C-G is Benign according to our data. Variant chr14-87993123-C-G is described in ClinVar as Benign. ClinVar VariationId is 92505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.038 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.42G>C	p.Ala14Ala	synonymous_variant	Exon 1 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.42G>C	p.Ala14Ala	synonymous_variant	Exon 1 of 17	1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17033

AN:

152168

Hom.:

1111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0945

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.117

AC:

22335

AN:

190218

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.0342

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.000810

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.142

AC:

204126

AN:

1433858

Hom.:

15584

Cov.:

AF XY:

0.141

AC XY:

100162

AN XY:

710602

show subpopulations

African (AFR)

AF:

0.0342

AC:

1130

AN:

33044

American (AMR)

AF:

0.140

AC:

5697

AN:

40790

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3008

AN:

25656

East Asian (EAS)

AF:

0.00125

AC:

AN:

38420

South Asian (SAS)

AF:

0.101

AC:

8319

AN:

82774

European-Finnish (FIN)

AF:

0.158

AC:

7773

AN:

49094

Middle Eastern (MID)

AF:

0.160

AC:

904

AN:

5660

European-Non Finnish (NFE)

AF:

0.154

AC:

169452

AN:

1099142

Other (OTH)

AF:

0.131

AC:

7795

AN:

59278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9689

19379

29068

38758

48447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5928

11856

17784

23712

29640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.112

AC:

17042

AN:

152280

Hom.:

1114

Cov.:

AF XY:

0.112

AC XY:

8368

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0396

AC:

1647

AN:

41556

American (AMR)

AF:

0.130

AC:

1994

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

414

AN:

3470

East Asian (EAS)

AF:

0.00232

AC:

AN:

5174

South Asian (SAS)

AF:

0.0944

AC:

456

AN:

4830

European-Finnish (FIN)

AF:

0.154

AC:

1638

AN:

10618

Middle Eastern (MID)

AF:

0.130

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.154

AC:

10492

AN:

68006

Other (OTH)

AF:

0.108

AC:

228

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

808

1617

2425

3234

4042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.118

Hom.:

448

Bravo

AF:

0.106

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 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. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 21, 2019

Natera, Inc.

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 26, 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

-0.74

CADD

Benign

8.1

(source)

DANN

Benign

0.73

PhyloP100

-0.038

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over