rs12105421

Variant names:

• chr2-102959630-C-T
• rs12105421
• ENST00000640575.2:c.470-6024C>T

Variant summary

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

The ENST00000640575.2(TMEM182):​c.470-6024C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,142 control chromosomes in the GnomAD database, including 630 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 0.078 (630 hom., cov: 32)
• Consequence: TMEM182 ENST00000640575.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

Genes affected

TMEM182 (HGNC:26391): (transmembrane protein 182) 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM182	ENST00000640575.2	c.470-6024C>T		intron_variant	Intron 4 of 5	5		ENSP00000492657.2

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11927 AN: 152024 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0785 AC: 11940 AN: 152142 Hom.: 630 Cov.: 32 AF XY: 0.0804 AC XY: 5979 AN XY: 74362

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.0403

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0539 Hom.: 78

Bravo AF: 0.0786

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12105421; hg19: chr2-103576088;