rs2540226

Positions:

• chr2-39731920-A-C
• chr2-39731920-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM178A	XM_024452702.2	c.401-3309A>C		intron_variant			XP_024308470.1
		n.39731920A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.553

Alfa AF: 0.507 Hom.: 24419

Bravo AF: 0.579

Asia WGS AF: 0.667 AC: 2319 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	0.86
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2540226; hg19: chr2-39959060;