rs727503068

Variant names:

• chr13-20192887-C-A
• NM_004004.6:c.-127G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-20192887-C-A
• chr13-20192887-C-G
• chr13-20192887-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004004.6(GJB2):​c.-127G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 714 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: GJB2 NM_004004.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

Genes affected

GJB2 (HGNC:4284): (gap junction protein beta 2) This gene encodes a member of the gap junction protein family. The gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels that facilitate the transfer of ions and small molecules between cells. The gap junction proteins, also known as connexins, purified from fractions of enriched gap junctions from different tissues differ. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene are responsible for as much as 50% of pre-lingual, recessive deafness. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJB2	NM_004004.6	c.-127G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000382848.5	NP_003995.2
GJB2	NM_004004.6	c.-127G>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000382848.5	NP_003995.2
GJB2	XM_011535049.3	c.-949G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		XP_011533351.1
GJB2	XM_011535049.3	c.-949G>T		5_prime_UTR_variant	Exon 1 of 2		XP_011533351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJB2	ENST00000382848.5	c.-127G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_004004.6	ENSP00000372299.4
GJB2	ENST00000382848.5	c.-127G>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_004004.6	ENSP00000372299.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00140 AC: 1 AN: 714 Hom.: 0 Cov.: 0 AF XY: 0.00204 AC XY: 1 AN XY: 490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-20767026;