Variant rs366615 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.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

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:

GALC (HGNC:):

GALC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.1670+60C>T		intron_variant		ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.1670+60C>T		intron_variant		1	NM_000153.4	ENSP00000261304.2		P54803-1

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

Gnomad4 AFR exome

AF:

0.611

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.484

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.455

GnomAD4 genome

AF:

0.492

AC:

74767

AN:

151812

Hom.:

19102

Cov.:

AF XY:

0.487

AC XY:

36159

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.491

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.333

Hom.:

1008

Bravo

AF:

0.489

Asia WGS

AF:

0.398

AC:

1385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

-0.80

CADD

Benign

DANN

Benign

0.73

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