rs3805787

Positions:

• chr6-121437761-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000282561.4(GJA1):​c.-17+1929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,090 control chromosomes in the GnomAD database, including 3,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3899 hom., cov: 32)
• Consequence: GJA1 ENST00000282561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

Genes affected

GJA1 (HGNC:4274): (gap junction protein alpha 1) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. The encoded protein is the major protein of gap junctions in the heart that are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. A related intronless pseudogene has been mapped to chromosome 5. Mutations in this gene have been associated with oculodentodigital dysplasia, autosomal recessive craniometaphyseal dysplasia and heart malformations. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA1	NM_000165.5	c.-17+1929A>G		intron_variant		ENST00000282561.4	NP_000156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA1	ENST00000282561.4	c.-17+1929A>G		intron_variant		1	NM_000165.5	ENSP00000282561	P1
GJA1	ENST00000647564.1	c.-17+36A>G		intron_variant				ENSP00000497565	P1
GJA1	ENST00000649003.1	c.-17+2101A>G		intron_variant				ENSP00000497283	P1
GJA1	ENST00000650427.1	c.-17+346A>G		intron_variant				ENSP00000497367	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30581 AN: 151972 Hom.: 3897 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 30585 AN: 152090 Hom.: 3899 Cov.: 32 AF XY: 0.206 AC XY: 15284 AN XY: 74354

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.210

Alfa AF: 0.236 Hom.: 5616

Bravo AF: 0.213

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs3805787; hg19: chr6-121758907; COSMIC: COSV56999333;