Variant 14-87933743-C-T 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.*989G>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 0.979 in 455,782 control chromosomes in the GnomAD database, including 218,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70035 hom., cov: 33)

Exomes 𝑓: 0.99 ( 148740 hom. )

Consequence

GALC
NM_000153.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.583

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=-0.93).

BP6

Variant 14-87933743-C-T is Benign according to our data. Variant chr14-87933743-C-T is described in ClinVar as [Benign]. Clinvar id is 314734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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.*989G>A		3_prime_UTR_variant	17/17	ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALC	ENST00000261304 linkuse as main transcript	c.*989G>A	3_prime_UTR_variant	17/17	1	NM_000153.4	ENSP00000261304.2	P54803-1
GALC	ENST00000544807 linkuse as main transcript	c.*230G>A	3_prime_UTR_variant	17/17	2		ENSP00000437513.2	P54803-5
GALC	ENST00000555000.5 linkuse as main transcript	n.*74+156G>A	intron_variant		2		ENSP00000450472.1	G3V255

Frequencies

GnomAD3 genomes

AF:

0.957

AC:

145606

AN:

152098

Hom.:

69995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

0.938

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.963

GnomAD4 exome

AF:

0.990

AC:

300389

AN:

303566

Hom.:

148740

Cov.:

AF XY:

0.991

AC XY:

154561

AN XY:

156042

show subpopulations

Gnomad4 AFR exome

AF:

0.849

Gnomad4 AMR exome

AF:

0.988

Gnomad4 ASJ exome

AF:

0.998

Gnomad4 EAS exome

AF:

0.958

Gnomad4 SAS exome

AF:

0.998

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.983

GnomAD4 genome

AF:

0.957

AC:

145706

AN:

152216

Hom.:

70035

Cov.:

AF XY:

0.958

AC XY:

71317

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.861

Gnomad4 AMR

AF:

0.984

Gnomad4 ASJ

AF:

0.998

Gnomad4 EAS

AF:

0.938

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.964

Alfa

AF:

0.983

Hom.:

23778

Bravo

AF:

0.950

Asia WGS

AF:

0.960

AC:

3340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.34

DANN

Benign

0.59

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