Variant chr14-87988566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000153.4(GALC):c.196-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,354,320 control chromosomes in the GnomAD database, including 243,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26971 hom., cov: 32)

Exomes 𝑓: 0.60 ( 216676 hom. )

Consequence

GALC
NM_000153.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.658

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=-0.93).

BP6

Variant 14-87988566-G-A is Benign according to our data. Variant chr14-87988566-G-A is described in ClinVar as [Benign]. Clinvar id is 255374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.196-43C>T		intron_variant		ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.196-43C>T		intron_variant		1	NM_000153.4	ENSP00000261304	P1	P54803-1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90205

AN:

151872

Hom.:

26963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.566

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.618

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.590

GnomAD3 exomes

AF:

0.622

AC:

152872

AN:

245826

Hom.:

48168

AF XY:

0.617

AC XY:

82574

AN XY:

133826

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.724

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.825

Gnomad SAS exome

AF:

0.593

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.599

AC:

719780

AN:

1202330

Hom.:

216676

Cov.:

AF XY:

0.598

AC XY:

366070

AN XY:

611976

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.718

Gnomad4 ASJ exome

AF:

0.591

Gnomad4 EAS exome

AF:

0.803

Gnomad4 SAS exome

AF:

0.599

Gnomad4 FIN exome

AF:

0.571

Gnomad4 NFE exome

AF:

0.586

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.594

AC:

90249

AN:

151990

Hom.:

26971

Cov.:

AF XY:

0.596

AC XY:

44246

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.565

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.584

Gnomad4 EAS

AF:

0.814

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.562

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.589

Hom.:

7926

Bravo

AF:

0.604

Asia WGS

AF:

0.615

AC:

2140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Galactosylceramide beta-galactosidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.6

DANN

Benign

0.61

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