ENST00000429432.5:c.-71+592G>A

Variant names:

• chr3-32106421-G-A
• rs13095243
• ENST00000429432.5:c.-71+592G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000429432.5(GPD1L):​c.-71+592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 297,808 control chromosomes in the GnomAD database, including 109,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54655 hom., cov: 33)
  • Exomes 𝑓: 0.86 (54762 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-32106421-G-A is Benign according to our data. Variant chr3-32106421-G-A is described in ClinVar as [Benign]. Clinvar id is 683540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPD1L	NM_015141.4	c.-291G>A		upstream_gene_variant		ENST00000282541.10	NP_055956.1
GPD1L	XM_006713068.3	c.-291G>A		upstream_gene_variant			XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000429432.5	c.-71+592G>A		intron_variant	Intron 1 of 3	4		ENSP00000393861.1
GPD1L	ENST00000282541.10	c.-291G>A		upstream_gene_variant		1	NM_015141.4	ENSP00000282541.6
GPD1L	ENST00000425459.5	c.-291G>A		upstream_gene_variant		4		ENSP00000408770.1
GPD1L	ENST00000428684.1	n.-291G>A		upstream_gene_variant		5		ENSP00000392199.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128301 AN: 152030 Hom.: 54639 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.855

GnomAD4 exome AF: 0.862 AC: 125618 AN: 145660 Hom.: 54762 AF XY: 0.864 AC XY: 64188 AN XY: 74256

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.870

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.862

GnomAD4 genome AF: 0.844 AC: 128362 AN: 152148 Hom.: 54655 Cov.: 33 AF XY: 0.843 AC XY: 62699 AN XY: 74372

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.848

Alfa AF: 0.876 Hom.: 7288

Bravo AF: 0.832

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.26
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13095243; hg19: chr3-32147913; COSMIC: COSV56993087;