Variant 14-87934106-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.*626C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,496,608 control chromosomes in the GnomAD database, including 166,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19129 hom., cov: 34)

Exomes 𝑓: 0.46 ( 146992 hom. )

Consequence

GALC
NM_000153.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.12

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=-0.8).

BP6

Variant 14-87934106-G-A is Benign according to our data. Variant chr14-87934106-G-A is described in ClinVar as [Benign]. Clinvar id is 314739.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.*626C>T		3_prime_UTR_variant	17/17	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 linkuse as main transcript	c.*626C>T	3_prime_UTR_variant	17/17	1	NM_000153.4	ENSP00000261304	P1	P54803-1
GALC	ENST00000544807.6 linkuse as main transcript	c.1744-107C>T	intron_variant		2		ENSP00000437513		P54803-5
GALC	ENST00000555000.5 linkuse as main transcript	c.1279-107C>T	intron_variant, NMD_transcript_variant		2		ENSP00000450472

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74806

AN:

151854

Hom.:

19099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.463

AC:

622699

AN:

1344636

Hom.:

146992

Cov.:

AF XY:

0.462

AC XY:

305847

AN XY:

661946

show subpopulations

Gnomad4 AFR exome

AF:

0.609

Gnomad4 AMR exome

AF:

0.328

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.459

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.493

AC:

74889

AN:

151972

Hom.:

19129

Cov.:

AF XY:

0.488

AC XY:

36245

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.495

Hom.:

4076

Bravo

AF:

0.489

Asia WGS

AF:

0.398

AC:

1382

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

-0.80

CADD

Benign

8.3

DANN

Benign

0.47

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