rs61732640

Variant names:

• chr1-34785239-G-A
• rs61732640
• NM_024009.3:c.477G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-34785239-G-A
• chr1-34785239-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024009.3(GJB3):​c.477G>A​(p.Pro159Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,613,878 control chromosomes in the GnomAD database, including 350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (162 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (188 hom.)
• Consequence: GJB3 NM_024009.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -5.55
• Publications: 1 publications found

Genes affected

GJB3 (HGNC:4285): (gap junction protein beta 3) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene can cause non-syndromic deafness or erythrokeratodermia variabilis, a skin disorder. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-34785239-G-A is Benign according to our data. Variant chr1-34785239-G-A is described in ClinVar as Benign. ClinVar VariationId is 163530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024009.3. 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
	GJB3	NM_024009.3	MANE Select	c.477G>A	p.Pro159Pro	synonymous	Exon 2 of 2	NP_076872.1	O75712
	GJB3	NM_001005752.2		c.477G>A	p.Pro159Pro	synonymous	Exon 2 of 2	NP_001005752.1	O75712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB3	ENST00000373366.3	TSL:1 MANE Select	c.477G>A	p.Pro159Pro	synonymous	Exon 2 of 2	ENSP00000362464.2	O75712
	GJB3	ENST00000373362.3	TSL:1	c.477G>A	p.Pro159Pro	synonymous	Exon 2 of 2	ENSP00000362460.3	O75712
	SMIM12	ENST00000426886.1	TSL:1	n.208-66830C>T		intron	N/A	ENSP00000429902.1	E5RH51

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3940 AN: 152026 Hom.: 161 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00976

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.00794 AC: 1995 AN: 251370 AF XY: 0.00598

Gnomad AFR exome AF: 0.0943

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00326 AC: 4758 AN: 1461734 Hom.: 188 Cov.: 34 AF XY: 0.00289 AC XY: 2099 AN XY: 727178

African (AFR) AF: 0.0937 AC: 3137 AN: 33474

American (AMR) AF: 0.00512 AC: 229 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 484 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000869 AC: 75 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.000275 AC: 306 AN: 1111960

Other (OTH) AF: 0.00828 AC: 500 AN: 60392

GnomAD4 genome AF: 0.0259 AC: 3946 AN: 152144 Hom.: 162 Cov.: 32 AF XY: 0.0254 AC XY: 1888 AN XY: 74388

African (AFR) AF: 0.0879 AC: 3647 AN: 41480

American (AMR) AF: 0.00975 AC: 149 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68000

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.0128 Hom.: 63

Bravo AF: 0.0296

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	not specified (3)
-	-	1	Erythrokeratodermia variabilis et progressiva 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.032
DANN	Benign	0.78
PhyloP100		-5.6
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: rs61732640; hg19: chr1-35250840;