rs11974610

Variant names:

• chr7-99930354-G-A
• rs11974610
• XM_047420329.1:c.-734C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GJC3	XM_047420329.1	c.-734C>T		5_prime_UTR_variant	Exon 1 of 3		XP_047276285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237640	ENST00000456499.1	n.327+636G>A		intron_variant	Intron 1 of 2	3
ENSG00000237640	ENST00000790901.1	n.380+636G>A		intron_variant	Intron 1 of 1
ENSG00000237640	ENST00000790904.1	n.172+9059G>A		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.542 AC: 22478 AN: 41438

American (AMR) AF: 0.226 AC: 3457 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.141 AC: 729 AN: 5164

South Asian (SAS) AF: 0.126 AC: 609 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1954 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13191 AN: 67976

Other (OTH) AF: 0.249 AC: 527 AN: 2114

Alfa AF: 0.220 Hom.: 17184

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
PhyloP100		-0.092

Splicing

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

Other links and lift over

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