rs2716734

Variant names:

• chr2-39720581-C-T
• rs2716734
• XM_024452702.2:c.401-14648C>T

Variant summary

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

The XM_024452702.2(TMEM178A):​c.401-14648C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,182 control chromosomes in the GnomAD database, including 2,234 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 0.11 (2234 hom., cov: 32)
• Consequence: TMEM178A XM_024452702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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: 0.113 AC: 17229 AN: 152064 Hom.: 2213 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.114 AC: 17290 AN: 152182 Hom.: 2234 Cov.: 32 AF XY: 0.110 AC XY: 8171 AN XY: 74400

African (AFR) AF: 0.321 AC: 13309 AN: 41486

American (AMR) AF: 0.0519 AC: 794 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4822

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2396 AN: 68012

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0553 Hom.: 2305

Bravo AF: 0.126

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2716734; hg19: chr2-39947721;