rs12432149

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 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 -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 VariationId is 92496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.551

AC:

136630

AN:

248100

AF XY:

0.552

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 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

African (AFR)

AF:

0.221

AC:

6994

AN:

31624

American (AMR)

AF:

0.664

AC:

29508

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

13023

AN:

25330

East Asian (EAS)

AF:

0.757

AC:

29541

AN:

39002

South Asian (SAS)

AF:

0.579

AC:

48467

AN:

83694

European-Finnish (FIN)

AF:

0.530

AC:

28228

AN:

53216

Middle Eastern (MID)

AF:

0.550

AC:

3046

AN:

5536

European-Non Finnish (NFE)

AF:

0.520

AC:

523465

AN:

1007192

Other (OTH)

AF:

0.528

AC:

29781

AN:

56446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14810

29620

44431

59241

74051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14472

28944

43416

57888

72360

<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:

0.460

AC:

69846

AN:

151816

Hom.:

17740

Cov.:

AF XY:

0.466

AC XY:

34566

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.242

AC:

10038

AN:

41428

American (AMR)

AF:

0.586

AC:

8922

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1760

AN:

3470

East Asian (EAS)

AF:

0.751

AC:

3845

AN:

5118

South Asian (SAS)

AF:

0.570

AC:

2750

AN:

4822

European-Finnish (FIN)

AF:

0.525

AC:

5547

AN:

10572

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35385

AN:

67858

Other (OTH)

AF:

0.468

AC:

988

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1797

3594

5391

7188

8985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.492

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

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

- -

Apr 03, 2013

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

- -

Galactosylceramide beta-galactosidase deficiency

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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. -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.024

(source)

DANN

Benign

0.26

PhyloP100

-2.0

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