ENST00000429432.5:c.-71+656T>G

Variant names:

• chr3-32106485-T-G
• rs6805518
• ENST00000429432.5:c.-71+656T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000429432.5(GPD1L):​c.-71+656T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 367,448 control chromosomes in the GnomAD database, including 143,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56171 hom., cov: 35)
  • Exomes 𝑓: 0.90 (87448 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.39
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Brugada syndrome 2

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-32106485-T-G is Benign according to our data. Variant chr3-32106485-T-G is described in ClinVar as Benign. ClinVar VariationId is 671016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	NM_015141.4	MANE Select	c.-227T>G		upstream_gene	N/A	NP_055956.1	Q8N335

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	ENST00000429432.5	TSL:4	c.-71+656T>G		intron	N/A	ENSP00000393861.1	C9K0P5
	GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.-227T>G		upstream_gene	N/A	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.-227T>G		upstream_gene	N/A	ENSP00000572908.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 129978 AN: 150264 Hom.: 56145 Cov.: 35

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.872

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.897 AC: 194804 AN: 217080 Hom.: 87448 Cov.: 3 AF XY: 0.898 AC XY: 99686 AN XY: 111020

African (AFR) AF: 0.750 AC: 4287 AN: 5716

American (AMR) AF: 0.928 AC: 5624 AN: 6060

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 6784 AN: 7516

East Asian (EAS) AF: 0.872 AC: 16867 AN: 19352

South Asian (SAS) AF: 0.913 AC: 2046 AN: 2240

European-Finnish (FIN) AF: 0.903 AC: 17383 AN: 19260

Middle Eastern (MID) AF: 0.829 AC: 909 AN: 1096

European-Non Finnish (NFE) AF: 0.905 AC: 128679 AN: 142112

Other (OTH) AF: 0.891 AC: 12225 AN: 13728

GnomAD4 genome AF: 0.865 AC: 130051 AN: 150368 Hom.: 56171 Cov.: 35 AF XY: 0.869 AC XY: 63892 AN XY: 73540

African (AFR) AF: 0.746 AC: 29684 AN: 39790

American (AMR) AF: 0.924 AC: 14117 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3137 AN: 3468

East Asian (EAS) AF: 0.858 AC: 4404 AN: 5130

South Asian (SAS) AF: 0.917 AC: 4428 AN: 4830

European-Finnish (FIN) AF: 0.912 AC: 9672 AN: 10608

Middle Eastern (MID) AF: 0.869 AC: 252 AN: 290

European-Non Finnish (NFE) AF: 0.907 AC: 61647 AN: 67974

Other (OTH) AF: 0.874 AC: 1831 AN: 2094

Alfa AF: 0.869 Hom.: 2903

Bravo AF: 0.850

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.73
PhyloP100		-2.4
PromoterAI		-0.12	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6805518; hg19: chr3-32147977;