rs1861243

Variant names:

• chr2-39729696-T-C
• rs1861243
• XM_024452702.2:c.401-5533T>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.401-5533T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,058 control chromosomes in the GnomAD database, including 31,037 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 0.62 (31037 hom., cov: 32)
• Consequence: TMEM178A XM_024452702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM178A	XM_024452702.2	c.401-5533T>C		intron_variant	Intron 1 of 1		XP_024308470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94107 AN: 151940 Hom.: 30977 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.620 AC: 94220 AN: 152058 Hom.: 31037 Cov.: 32 AF XY: 0.622 AC XY: 46214 AN XY: 74322

African (AFR) AF: 0.833 AC: 34595 AN: 41508

American (AMR) AF: 0.651 AC: 9939 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3466

East Asian (EAS) AF: 0.837 AC: 4325 AN: 5168

South Asian (SAS) AF: 0.579 AC: 2787 AN: 4812

European-Finnish (FIN) AF: 0.533 AC: 5634 AN: 10564

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33432 AN: 67948

Other (OTH) AF: 0.603 AC: 1274 AN: 2112

Alfa AF: 0.568 Hom.: 3242

Bravo AF: 0.642

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs1861243; hg19: chr2-39956836;