Variant chr14-87982181-A-G 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.621+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,356,700 control chromosomes in the GnomAD database, including 13,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1144 hom., cov: 32)

Exomes 𝑓: 0.14 ( 12260 hom. )

Consequence

GALC
NM_000153.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.32

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=-0.88).

BP6

Variant 14-87982181-A-G is Benign according to our data. Variant chr14-87982181-A-G is described in ClinVar as [Benign]. Clinvar id is 255379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87982181-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 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.621+24T>C		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.621+24T>C		intron_variant		1	NM_000153.4	ENSP00000261304	P1	P54803-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17187

AN:

152068

Hom.:

1141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.125

AC:

28975

AN:

232122

Hom.:

2116

AF XY:

0.125

AC XY:

15756

AN XY:

126426

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.00101

Gnomad SAS exome

AF:

0.0959

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.136

AC:

164109

AN:

1204514

Hom.:

12260

Cov.:

AF XY:

0.136

AC XY:

82910

AN XY:

610656

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.00117

Gnomad4 SAS exome

AF:

0.0970

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.113

AC:

17196

AN:

152186

Hom.:

1144

Cov.:

AF XY:

0.113

AC XY:

8440

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0951

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.139

Hom.:

317

Bravo

AF:

0.107

Asia WGS

AF:

0.0550

AC:

190

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

-0.88

CADD

Benign

1.9

DANN

Benign

0.62

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