rs7333214

Variant names:

• chr13-20222358-C-A
• rs7333214
• NM_001110219.3:c.*337G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-20222358-C-A
• chr13-20222358-C-G
• chr13-20222358-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001110219.3(GJB6):​c.*337G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 229,700 control chromosomes in the GnomAD database, including 7,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6113 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1218 hom.)
• Consequence: GJB6 NM_001110219.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.715
• Publications: 13 publications found

Genes affected

GJB6 (HGNC:4288): (gap junction protein beta 6) Gap junctions allow the transport of ions and metabolites between the cytoplasm of adjacent cells. They are formed by two hemichannels, made up of six connexin proteins assembled in groups. Each connexin protein has four transmembrane segments, two extracellular loops, a cytoplasmic loop formed between the two inner transmembrane segments, and the N- and C-terminus both being in the cytoplasm. The specificity of the gap junction is determined by which connexin proteins comprise the hemichannel. In the past, connexin protein names were based on their molecular weight, however the new nomenclature uses sequential numbers based on which form (alpha or beta) of the gap junction is present. This gene encodes one of the connexin proteins. Mutations in this gene have been found in some forms of deafness and in some families with hidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]

GJB6 Gene-Disease associations (from GenCC):

• Clouston syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen, Ambry Genetics, G2P
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• KID syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nonsyndromic hearing loss 3B

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive nonsyndromic hearing loss 1B

  Inheritance: AR Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 13-20222358-C-A is Benign according to our data. Variant chr13-20222358-C-A is described in ClinVar as Benign. ClinVar VariationId is 311376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB6	NM_001110219.3	MANE Select	c.*337G>T		3_prime_UTR	Exon 5 of 5	NP_001103689.1	O95452
	GJB6	NM_001110220.3		c.*337G>T		3_prime_UTR	Exon 4 of 4	NP_001103690.1	O95452
	GJB6	NM_001110221.3		c.*337G>T		3_prime_UTR	Exon 3 of 3	NP_001103691.1	O95452

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB6	ENST00000647029.1	MANE Select	c.*337G>T		3_prime_UTR	Exon 5 of 5	ENSP00000493834.1	O95452
	GJB6	ENST00000241124.11	TSL:1	c.*337G>T		3_prime_UTR	Exon 3 of 3	ENSP00000241124.6	O95452
	GJB6	ENST00000400065.7	TSL:1	c.*337G>T		3_prime_UTR	Exon 3 of 3	ENSP00000382938.3	O95452

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37101 AN: 151990 Hom.: 6087 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.155 AC: 12004 AN: 77590 Hom.: 1218 Cov.: 0 AF XY: 0.151 AC XY: 6065 AN XY: 40286

African (AFR) AF: 0.441 AC: 979 AN: 2220

American (AMR) AF: 0.124 AC: 550 AN: 4420

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 613 AN: 2460

East Asian (EAS) AF: 0.281 AC: 1346 AN: 4794

South Asian (SAS) AF: 0.0886 AC: 524 AN: 5914

European-Finnish (FIN) AF: 0.0903 AC: 360 AN: 3986

Middle Eastern (MID) AF: 0.188 AC: 58 AN: 308

European-Non Finnish (NFE) AF: 0.138 AC: 6728 AN: 48818

Other (OTH) AF: 0.181 AC: 846 AN: 4670

GnomAD4 genome AF: 0.244 AC: 37178 AN: 152110 Hom.: 6113 Cov.: 32 AF XY: 0.240 AC XY: 17836 AN XY: 74360

African (AFR) AF: 0.472 AC: 19562 AN: 41454

American (AMR) AF: 0.164 AC: 2503 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1353 AN: 5176

South Asian (SAS) AF: 0.115 AC: 553 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10586

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10524 AN: 68006

Other (OTH) AF: 0.226 AC: 477 AN: 2114

Alfa AF: 0.188 Hom.: 9505

Bravo AF: 0.263

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hidrotic ectodermal dysplasia syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.3
DANN	Benign	0.55
PhyloP100		0.71
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: rs7333214; hg19: chr13-20796497;