rs12105421

Positions:

• chr2-102959630-C-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM182	ENST00000640575.2	c.470-6024C>T		intron_variant		5

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;