1-34755129-A-G

Position:

• chr1-34755129-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005268.4(GJB5):​c.-91A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,638 control chromosomes in the GnomAD database, including 20,947 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 0.50 (20914 hom., cov: 34)
  • Exomes 𝑓: 0.38 (33 hom.)
• Consequence: GJB5 NM_005268.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

Genes affected

GJB5 (HGNC:4287): (gap junction protein beta 5) This gene encodes a member of the beta-type (group I) connexin family. The encoded protein is a gap junction protein involved in intercellular communication related to epidermal differentiation and environmental sensing. This gene has been linked to non-small cell lung cancer. [provided by RefSeq, Nov 2012]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB5	NM_005268.4	c.-91A>G		5_prime_UTR_variant	1/2	ENST00000338513.1	NP_005259.1
GJB5	XM_005270751.4	c.-88A>G		5_prime_UTR_variant	1/2		XP_005270808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB5	ENST00000338513	c.-91A>G		5_prime_UTR_variant	1/2	1	NM_005268.4	ENSP00000340811.1
SMIM12	ENST00000426886.1	n.208-36720T>C		intron_variant		1		ENSP00000429902.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75416 AN: 152098 Hom.: 20881 Cov.: 34

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.377 AC: 159 AN: 422 Hom.: 33 Cov.: 0 AF XY: 0.377 AC XY: 122 AN XY: 324

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.496 AC: 75498 AN: 152216 Hom.: 20914 Cov.: 34 AF XY: 0.492 AC XY: 36640 AN XY: 74430

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.474

Alfa AF: 0.430 Hom.: 6539

Bravo AF: 0.514

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.86

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: rs2275229; hg19: chr1-35220730; COSMIC: COSV58355762; COSMIC: COSV58355762;