Variant 14-87933279-T-C 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.*1453A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,306 control chromosomes in the GnomAD database, including 19,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19114 hom., cov: 32)

Exomes 𝑓: 0.53 ( 62 hom. )

Consequence

GALC
NM_000153.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.77

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=-0.9).

BP6

Variant 14-87933279-T-C is Benign according to our data. Variant chr14-87933279-T-C is described in ClinVar as [Benign]. Clinvar id is 314729.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.*1453A>G		3_prime_UTR_variant	17/17	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.*1453A>G		3_prime_UTR_variant	17/17	1	NM_000153.4	ENSP00000261304	P1	P54803-1
GALC	ENST00000555000.5 linkuse as main transcript	c.*74+620A>G		intron_variant, NMD_transcript_variant		2		ENSP00000450472

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74744

AN:

151742

Hom.:

19084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.534

AC:

238

AN:

446

Hom.:

Cov.:

AF XY:

0.541

AC XY:

145

AN XY:

268

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.535

Gnomad4 NFE exome

AF:

0.600

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.493

AC:

74827

AN:

151860

Hom.:

19114

Cov.:

AF XY:

0.488

AC XY:

36221

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.491

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.470

Hom.:

17337

Bravo

AF:

0.489

Asia WGS

AF:

0.397

AC:

1381

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

-0.90

CADD

Benign

0.17

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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