Variant rs72546650 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000282541.10(GPD1L):c.366+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,620 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 5 hom. )

Consequence

GPD1L
ENST00000282541.10 splice_region, intron

Scores

Splicing: ADA: 0.00001204

Clinical Significance

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

Conservation

PhyloP100: 0.398

Variant links:

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GPD1L 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=-0.85).

BP6

Variant 3-32138735-G-A is Benign according to our data. Variant chr3-32138735-G-A is described in ClinVar as [Benign]. Clinvar id is 190761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-32138735-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00591 (900/152206) while in subpopulation AFR AF= 0.0199 (825/41526). AF 95% confidence interval is 0.0187. There are 11 homozygotes in gnomad4. There are 431 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 900 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1L	NM_015141.4 linkuse as main transcript	c.366+8G>A		splice_region_variant, intron_variant		ENST00000282541.10	NP_055956.1
GPD1L	XM_006713068.3 linkuse as main transcript	c.226-1493G>A		intron_variant			XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000282541.10 linkuse as main transcript	c.366+8G>A		splice_region_variant, intron_variant		1	NM_015141.4	ENSP00000282541	P1

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00164

AC:

410

AN:

250666

Hom.:

AF XY:

0.00123

AC XY:

166

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000620

AC:

906

AN:

1461414

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00591

AC:

900

AN:

152206

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

431

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.00743

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 28, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.76

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0020

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