rs11974610

Positions:

• chr7-99930354-G-A

Variant summary

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

The XM_047420329.1(GJC3):​c.-734C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,036 control chromosomes in the GnomAD database, including 8,245 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 0.29 (8245 hom., cov: 32)
• Consequence: GJC3 XM_047420329.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

GJC3 (HGNC:17495): (gap junction protein gamma 3) This gene encodes a gap junction protein. The encoded protein, also known as a connexin, plays a role in formation of gap junctions, which provide direct connections between neighboring cells. Mutations in this gene have been reported to be associated with nonsyndromic hearing loss.[provided by RefSeq, Feb 2010]

ENSG00000237640 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJC3	XM_047420329.1	c.-734C>T		5_prime_UTR_variant	1/3		XP_047276285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000237640	ENST00000456499.1	n.327+636G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43600 AN: 151918 Hom.: 8222 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.287 AC: 43662 AN: 152036 Hom.: 8245 Cov.: 32 AF XY: 0.281 AC XY: 20919 AN XY: 74322

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.249

Alfa AF: 0.202 Hom.: 5828

Bravo AF: 0.302

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11974610; hg19: chr7-99527977; COSMIC: COSV57210426;