NM_198568.3:c.-27-13764C>T

Variant names:

• chr6-87298703-G-A
• rs440296
• NM_198568.3:c.-27-13764C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

HSPD1P10 (HGNC:35131): (heat shock protein family D (Hsp60) member 1 pseudogene 10)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198568.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB7	NM_198568.3	MANE Select	c.-27-13764C>T		intron	N/A	NP_940970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB7	ENST00000525899.6	TSL:1 MANE Select	c.-27-13764C>T		intron	N/A	ENSP00000435355.1
	HSPD1P10	ENST00000404829.2	TSL:6	n.-69G>A		upstream_gene	N/A

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

African (AFR) AF: 0.373 AC: 118 AN: 316

American (AMR) AF: 0.548 AC: 725 AN: 1322

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 200 AN: 466

East Asian (EAS) AF: 0.438 AC: 268 AN: 612

South Asian (SAS) AF: 0.492 AC: 1272 AN: 2586

European-Finnish (FIN) AF: 0.377 AC: 2178 AN: 5776

Middle Eastern (MID) AF: 0.490 AC: 50 AN: 102

European-Non Finnish (NFE) AF: 0.371 AC: 5335 AN: 14386

Other (OTH) AF: 0.409 AC: 565 AN: 1382

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

African (AFR) AF: 0.402 AC: 16667 AN: 41464

American (AMR) AF: 0.529 AC: 8084 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1432 AN: 3462

East Asian (EAS) AF: 0.460 AC: 2382 AN: 5178

South Asian (SAS) AF: 0.470 AC: 2265 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3818 AN: 10536

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25828 AN: 67968

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.388 Hom.: 1502

Bravo AF: 0.421

Asia WGS AF: 0.459 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.95
DANN	Benign	0.34
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs440296; hg19: chr6-88008421;