6-121435882-C-T

Position:

• chr6-121435882-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000165.5(GJA1):​c.-17+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,090 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (199 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GJA1 NM_000165.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-121435882-C-T is Benign according to our data. Variant chr6-121435882-C-T is described in ClinVar as [Benign]. Clinvar id is 1232249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA1	NM_000165.5	c.-17+50C>T		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+50C>T		intron_variant		1	NM_000165.5	ENSP00000282561	P1
GJA1	ENST00000649003.1	c.-17+222C>T		intron_variant				ENSP00000497283	P1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3826 AN: 151972 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.00399

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0191

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0252 AC: 3828 AN: 152090 Hom.: 199 Cov.: 32 AF XY: 0.0299 AC XY: 2226 AN XY: 74344

Gnomad4 AFR AF: 0.00405

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0181 Hom.: 7

Bravo AF: 0.0219

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.86

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: rs79597379; hg19: chr6-121757028;