2-39731920-A-C

Variant names:

• chr2-39731920-A-C
• rs2540226
• XM_024452702.2:c.401-3309A>C

Variant summary

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

The XM_024452702.2(TMEM178A):​c.401-3309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,956 control chromosomes in the GnomAD database, including 25,056 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 0.57 (25056 hom., cov: 31)
• Consequence: TMEM178A XM_024452702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 17 publications found

Genes affected

TMEM178A (HGNC:28517): (transmembrane protein 178A) Predicted to be involved in negative regulation of osteoclast differentiation and regulation of cytosolic calcium ion concentration. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85929 AN: 151838 Hom.: 25017 Cov.: 31

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.566 AC: 86016 AN: 151956 Hom.: 25056 Cov.: 31 AF XY: 0.569 AC XY: 42243 AN XY: 74268

African (AFR) AF: 0.672 AC: 27853 AN: 41440

American (AMR) AF: 0.611 AC: 9325 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3470

East Asian (EAS) AF: 0.769 AC: 3970 AN: 5160

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4810

European-Finnish (FIN) AF: 0.532 AC: 5619 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 135 AN: 290

European-Non Finnish (NFE) AF: 0.489 AC: 33195 AN: 67940

Other (OTH) AF: 0.553 AC: 1167 AN: 2112

Alfa AF: 0.524 Hom.: 44262

Bravo AF: 0.579

Asia WGS AF: 0.667 AC: 2319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.54
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs2540226; hg19: chr2-39959060;