7-150802699-T-C

Variant names:

• chr7-150802699-T-C
• rs714885
• NM_018487.3:c.285+374T>C

Variant summary

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

The NM_018487.3(TMEM176A):​c.285+374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,056,412 control chromosomes in the GnomAD database, including 230,775 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 0.66 (33810 hom., cov: 32)
  • Exomes 𝑓: 0.66 (196965 hom.)
• Consequence: TMEM176A NM_018487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 9 publications found

Genes affected

TMEM176A (HGNC:24930): (transmembrane protein 176A) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be integral component of 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 (SAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM176A	NM_018487.3	c.285+374T>C		intron_variant	Intron 3 of 6	ENST00000004103.8	NP_060957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8	c.285+374T>C		intron_variant	Intron 3 of 6	1	NM_018487.3	ENSP00000004103.3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101000 AN: 151900 Hom.: 33779 Cov.: 32

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.659 AC: 595718 AN: 904394 Hom.: 196965 Cov.: 23 AF XY: 0.660 AC XY: 278182 AN XY: 421692

African (AFR) AF: 0.634 AC: 11704 AN: 18470

American (AMR) AF: 0.648 AC: 3362 AN: 5192

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 4999 AN: 7362

East Asian (EAS) AF: 0.746 AC: 5543 AN: 7428

South Asian (SAS) AF: 0.749 AC: 17259 AN: 23030

European-Finnish (FIN) AF: 0.676 AC: 2356 AN: 3484

Middle Eastern (MID) AF: 0.776 AC: 1528 AN: 1970

European-Non Finnish (NFE) AF: 0.655 AC: 527674 AN: 805668

Other (OTH) AF: 0.670 AC: 21293 AN: 31790

GnomAD4 genome AF: 0.665 AC: 101081 AN: 152018 Hom.: 33810 Cov.: 32 AF XY: 0.668 AC XY: 49639 AN XY: 74292

African (AFR) AF: 0.638 AC: 26442 AN: 41438

American (AMR) AF: 0.664 AC: 10141 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2392 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3795 AN: 5162

South Asian (SAS) AF: 0.761 AC: 3669 AN: 4820

European-Finnish (FIN) AF: 0.692 AC: 7296 AN: 10548

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45224 AN: 67982

Other (OTH) AF: 0.696 AC: 1469 AN: 2112

Alfa AF: 0.668 Hom.: 17300

Bravo AF: 0.662

Asia WGS AF: 0.724 AC: 2518 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	1.6
DANN	Benign	0.62
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs714885; hg19: chr7-150499787;