rs2093185

Variant names:

• chr1-34758711-T-G
• rs2093185
• ENST00000426886.1:n.208-40302A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000426886.1(SMIM12):​n.208-40302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,060 control chromosomes in the GnomAD database, including 21,301 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 (21301 hom., cov: 32)
• Consequence: SMIM12 ENST00000426886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 5 publications found

Genes affected

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

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJB5	NM_005268.4	c.*559T>G		downstream_gene_variant		ENST00000338513.1	NP_005259.1
GJB5	XM_005270751.4	c.*559T>G		downstream_gene_variant			XP_005270808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM12	ENST00000426886.1	n.208-40302A>C		intron_variant	Intron 2 of 4	1		ENSP00000429902.1
GJB5	ENST00000338513.1	c.*559T>G		downstream_gene_variant		1	NM_005268.4	ENSP00000340811.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75999 AN: 151942 Hom.: 21266 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.500 AC: 76082 AN: 152060 Hom.: 21301 Cov.: 32 AF XY: 0.496 AC XY: 36863 AN XY: 74342

African (AFR) AF: 0.768 AC: 31823 AN: 41456

American (AMR) AF: 0.413 AC: 6308 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3468

East Asian (EAS) AF: 0.535 AC: 2755 AN: 5154

South Asian (SAS) AF: 0.410 AC: 1971 AN: 4808

European-Finnish (FIN) AF: 0.335 AC: 3544 AN: 10586

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26659 AN: 67980

Other (OTH) AF: 0.474 AC: 1004 AN: 2116

Alfa AF: 0.430 Hom.: 56788

Bravo AF: 0.520

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2093185; hg19: chr1-35224312; COSMIC: COSV58355766;