dbSNP rs366615: GALC:c.1670+60C>T (chr14-87945493-G-A) – ACMG Classification: Benign (-20 pts)

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.1670+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,238,394 control chromosomes in the GnomAD database, including 136,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19102 hom., cov: 32)

Exomes 𝑓: 0.46 ( 117643 hom. )

Consequence

GALC
NM_000153.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0990

Publications

10 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: Laboratory for Molecular Medicine, Genomics England PanelApp, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

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=-0.8).

BP6

Variant 14-87945493-G-A is Benign according to our data. Variant chr14-87945493-G-A is described in ClinVar as Benign. ClinVar VariationId is 1177549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000153.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALC	NM_000153.4	MANE Select	c.1670+60C>T	intron	N/A	NP_000144.2	P54803-1
GALC	NM_001201401.2		c.1601+60C>T	intron	N/A	NP_001188330.1	P54803-3
GALC	NM_001201402.2		c.1592+60C>T	intron	N/A	NP_001188331.1	P54803-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALC	ENST00000261304.7	TSL:1 MANE Select	c.1670+60C>T	intron	N/A	ENSP00000261304.2	P54803-1
GALC	ENST00000921945.1		c.1631+60C>T	intron	N/A	ENSP00000592004.1
GALC	ENST00000950382.1		c.1604+60C>T	intron	N/A	ENSP00000620441.1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74684

AN:

151694

Hom.:

19072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.486

GnomAD4 exome

AF:

0.459

AC:

498892

AN:

1086582

Hom.:

117643

AF XY:

0.458

AC XY:

256016

AN XY:

558468

show subpopulations

African (AFR)

AF:

0.611

AC:

15906

AN:

26032

American (AMR)

AF:

0.325

AC:

14320

AN:

44016

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

11475

AN:

23718

East Asian (EAS)

AF:

0.195

AC:

7401

AN:

37926

South Asian (SAS)

AF:

0.417

AC:

32697

AN:

78402

European-Finnish (FIN)

AF:

0.470

AC:

24933

AN:

53100

Middle Eastern (MID)

AF:

0.439

AC:

2166

AN:

4936

European-Non Finnish (NFE)

AF:

0.478

AC:

368173

AN:

770540

Other (OTH)

AF:

0.455

AC:

21821

AN:

47912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13901

27802

41703

55604

69505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9002

18004

27006

36008

45010

<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:

0.492

AC:

74767

AN:

151812

Hom.:

19102

Cov.:

AF XY:

0.487

AC XY:

36159

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.603

AC:

24990

AN:

41446

American (AMR)

AF:

0.396

AC:

6025

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1701

AN:

3466

East Asian (EAS)

AF:

0.185

AC:

951

AN:

5128

South Asian (SAS)

AF:

0.424

AC:

2042

AN:

4816

European-Finnish (FIN)

AF:

0.475

AC:

5005

AN:

10534

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.478

AC:

32428

AN:

67890

Other (OTH)

AF:

0.490

AC:

1033

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1888

3775

5663

7550

9438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.333

Hom.:

1008

Bravo

AF:

0.489

Asia WGS

AF:

0.398

AC:

1385

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Galactosylceramide beta-galactosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.099

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over