rs440296

Positions:

• chr6-87298703-G-A
• chr6-87298703-G-T

Variant summary

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

The NM_198568.3(GJB7):​c.-27-13764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 178,976 control chromosomes in the GnomAD database, including 15,146 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 0.41 (12881 hom., cov: 32)
  • Exomes 𝑓: 0.40 (2265 hom.)
• Consequence: GJB7 NM_198568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

GJB7 (HGNC:16690): (gap junction protein beta 7) Connexins, such as GJB7, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB7	NM_198568.3	c.-27-13764C>T		intron_variant		ENST00000525899.6	NP_940970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB7	ENST00000525899.6	c.-27-13764C>T		intron_variant		1	NM_198568.3	ENSP00000435355	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61846 AN: 151910 Hom.: 12868 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.397 AC: 10711 AN: 26948 Hom.: 2265 AF XY: 0.403 AC XY: 5618 AN XY: 13932

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.407 AC: 61905 AN: 152028 Hom.: 12881 Cov.: 32 AF XY: 0.410 AC XY: 30491 AN XY: 74328

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.411

Alfa AF: 0.387 Hom.: 1436

Bravo AF: 0.421

Asia WGS AF: 0.459 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.95
DANN	Benign	0.34

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: rs440296; hg19: chr6-88008421;