6-87284268-T-TA

Position:

• chr6-87284268-T-TA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_198568.3(GJB7):​c.644dupT​(p.Leu215fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,613,634 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: GJB7 NM_198568.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450

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]

LOC124901356 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-87284268-T-TA is Benign according to our data. Variant chr6-87284268-T-TA is described in ClinVar as [Benign]. Clinvar id is 776141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB7	NM_198568.3	c.644dupT	p.Leu215fs	frameshift_variant	3/3	ENST00000525899.6	NP_940970.1
LOC124901356	XR_007059667.1	n.692-355dupA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB7	ENST00000525899.6	c.644dupT	p.Leu215fs	frameshift_variant	3/3	1	NM_198568.3	ENSP00000435355.1

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 427 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00954

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.000885 AC: 222 AN: 250910 Hom.: 0 AF XY: 0.000597 AC XY: 81 AN XY: 135644

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000323 AC: 472 AN: 1461358 Hom.: 2 Cov.: 30 AF XY: 0.000265 AC XY: 193 AN XY: 727012

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.000762

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.00282 AC: 429 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00269 AC XY: 200 AN XY: 74460

Gnomad4 AFR AF: 0.00956

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00162 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Labcorp Genetics (formerly Invitae), Labcorp

Oct 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs532131782; hg19: chr6-87993986;