Variant 14-87933606-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000153.4(GALC):c.*1126G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 178,520 control chromosomes in the GnomAD database, including 1,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1141 hom., cov: 33)

Exomes 𝑓: 0.14 ( 304 hom. )

Consequence

GALC
NM_000153.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-87933606-C-T is Benign according to our data. Variant chr14-87933606-C-T is described in ClinVar as [Benign]. Clinvar id is 314733.Status of the report is criteria_provided_single_submitter, 1 stars.

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	UniProt
GALC	NM_000153.4 linkuse as main transcript	c.*1126G>A		3_prime_UTR_variant	17/17	ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.*1126G>A		3_prime_UTR_variant	17/17	1	NM_000153.4	P1	P54803-1
GALC	ENST00000555000.5 linkuse as main transcript	c.*74+293G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16717

AN:

151996

Hom.:

1139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0955

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.142

AC:

3743

AN:

26404

Hom.:

304

Cov.:

AF XY:

0.147

AC XY:

1950

AN XY:

13270

show subpopulations

Gnomad4 AFR exome

AF:

0.0374

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.00583

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.110

AC:

16717

AN:

152116

Hom.:

1141

Cov.:

AF XY:

0.110

AC XY:

8158

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0949

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.145

Hom.:

393

Bravo

AF:

0.102

Asia WGS

AF:

0.0560

AC:

195

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.65

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