rs1077601

Variant names:

• chr3-32106593-C-T
• rs1077601
• ENST00000429432.5:c.-71+764C>T

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+764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,000,430 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (199 hom., cov: 33)
  • Exomes 𝑓: 0.035 (599 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-0.49).
• BP6: Variant 3-32106593-C-T is Benign according to our data. Variant chr3-32106593-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0797 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.-119C>T		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+764C>T		intron	N/A	ENSP00000393861.1	C9K0P5
	GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.-119C>T		upstream_gene	N/A	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.-119C>T		upstream_gene	N/A	ENSP00000572908.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7058 AN: 151952 Hom.: 199 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0459

GnomAD4 exome AF: 0.0348 AC: 29519 AN: 848370 Hom.: 599 Cov.: 11 AF XY: 0.0353 AC XY: 14719 AN XY: 417370

African (AFR) AF: 0.0620 AC: 1084 AN: 17484

American (AMR) AF: 0.101 AC: 942 AN: 9290

Ashkenazi Jewish (ASJ) AF: 0.0466 AC: 682 AN: 14624

East Asian (EAS) AF: 0.0265 AC: 662 AN: 24998

South Asian (SAS) AF: 0.0514 AC: 1449 AN: 28174

European-Finnish (FIN) AF: 0.0373 AC: 1215 AN: 32586

Middle Eastern (MID) AF: 0.0615 AC: 174 AN: 2830

European-Non Finnish (NFE) AF: 0.0317 AC: 21673 AN: 682696

Other (OTH) AF: 0.0459 AC: 1638 AN: 35688

GnomAD4 genome AF: 0.0465 AC: 7066 AN: 152060 Hom.: 199 Cov.: 33 AF XY: 0.0477 AC XY: 3549 AN XY: 74364

African (AFR) AF: 0.0560 AC: 2326 AN: 41546

American (AMR) AF: 0.0835 AC: 1276 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.0221 AC: 113 AN: 5102

South Asian (SAS) AF: 0.0445 AC: 215 AN: 4830

European-Finnish (FIN) AF: 0.0421 AC: 445 AN: 10578

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0337 AC: 2292 AN: 67934

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0430 Hom.: 24

Bravo AF: 0.0502

Asia WGS AF: 0.0540 AC: 185 AN: 3456

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	-0.49
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		-0.15
PromoterAI		-0.046	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1077601; hg19: chr3-32148085;