1-34760655-T-C

Position:

• chr1-34760655-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153212.3(GJB4):​c.-322-278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,068 control chromosomes in the GnomAD database, including 21,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (21497 hom., cov: 32)
• Consequence: GJB4 NM_153212.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.737

Genes affected

GJB4 (HGNC:4286): (gap junction protein beta 4) This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009]

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-34760655-T-C is Benign according to our data. Variant chr1-34760655-T-C is described in ClinVar as [Benign]. Clinvar id is 1247767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB4	NM_153212.3	c.-322-278T>C		intron_variant		ENST00000339480.3	NP_694944.1
GJB4	XM_011540679.3	c.-322-278T>C		intron_variant			XP_011538981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB4	ENST00000339480.3	c.-322-278T>C		intron_variant		2	NM_153212.3	ENSP00000345868	P1
SMIM12	ENST00000426886.1	c.208-42246A>G		intron_variant, NMD_transcript_variant		1		ENSP00000429902

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76370 AN: 151950 Hom.: 21461 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.503 AC: 76457 AN: 152068 Hom.: 21497 Cov.: 32 AF XY: 0.499 AC XY: 37059 AN XY: 74338

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.476

Alfa AF: 0.468 Hom.: 2740

Bravo AF: 0.522

Asia WGS AF: 0.460 AC: 1600 AN: 3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.43

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: rs1998177; hg19: chr1-35226256; COSMIC: COSV58355769; COSMIC: COSV58355769;