rs741067

Positions:

• chr7-150803367-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018487.3(TMEM176A):​c.286-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,541,644 control chromosomes in the GnomAD database, including 354,808 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 0.70 (37596 hom., cov: 32)
  • Exomes 𝑓: 0.67 (317212 hom.)
• Consequence: TMEM176A NM_018487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

TMEM176A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM176A	NM_018487.3	c.286-33A>G		intron_variant		ENST00000004103.8	NP_060957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8	c.286-33A>G		intron_variant		1	NM_018487.3	ENSP00000004103.3

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106438 AN: 151936 Hom.: 37558 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.722

GnomAD3 exomes AF: 0.698 AC: 130339 AN: 186824 Hom.: 45649 AF XY: 0.699 AC XY: 68803 AN XY: 98436

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.669

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.770

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.665

Gnomad OTH exome AF: 0.695

GnomAD4 exome AF: 0.674 AC: 936753 AN: 1389590 Hom.: 317212 Cov.: 57 AF XY: 0.677 AC XY: 463493 AN XY: 684776

Gnomad4 AFR exome AF: 0.759

Gnomad4 AMR exome AF: 0.672

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 0.689

GnomAD4 genome AF: 0.701 AC: 106535 AN: 152054 Hom.: 37596 Cov.: 32 AF XY: 0.703 AC XY: 52236 AN XY: 74312

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.723

Alfa AF: 0.677 Hom.: 60678

Bravo AF: 0.703

Asia WGS AF: 0.760 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs741067; hg19: chr7-150500455;