NM_018487.3:c.286-33A>G

Variant names:

• chr7-150803367-A-G
• rs741067
• NM_018487.3:c.286-33A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

TMEM176B (HGNC:29596): (transmembrane protein 176B) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be located in nuclear membrane. 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018487.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM176A	NM_018487.3	MANE Select	c.286-33A>G		intron	N/A	NP_060957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM176A	ENST00000004103.8	TSL:1 MANE Select	c.286-33A>G		intron	N/A	ENSP00000004103.3	Q96HP8
	TMEM176A	ENST00000855170.1		c.433A>G	p.Thr145Ala	missense	Exon 4 of 7	ENSP00000525229.1
	TMEM176A	ENST00000855172.1		c.433A>G	p.Thr145Ala	missense	Exon 4 of 7	ENSP00000525231.1

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

GnomAD2 exomes AF: 0.698 AC: 130339 AN: 186824 AF XY: 0.699

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 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

African (AFR) AF: 0.759 AC: 23447 AN: 30906

American (AMR) AF: 0.672 AC: 21679 AN: 32260

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 14257 AN: 20790

East Asian (EAS) AF: 0.818 AC: 32133 AN: 39286

South Asian (SAS) AF: 0.765 AC: 55297 AN: 72240

European-Finnish (FIN) AF: 0.686 AC: 34839 AN: 50764

Middle Eastern (MID) AF: 0.767 AC: 4140 AN: 5398

European-Non Finnish (NFE) AF: 0.658 AC: 711418 AN: 1080578

Other (OTH) AF: 0.689 AC: 39543 AN: 57368

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

African (AFR) AF: 0.753 AC: 31211 AN: 41474

American (AMR) AF: 0.676 AC: 10338 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2394 AN: 3472

East Asian (EAS) AF: 0.789 AC: 4070 AN: 5158

South Asian (SAS) AF: 0.772 AC: 3719 AN: 4820

European-Finnish (FIN) AF: 0.691 AC: 7301 AN: 10560

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45310 AN: 67966

Other (OTH) AF: 0.723 AC: 1529 AN: 2114

Alfa AF: 0.682 Hom.: 100916

Bravo AF: 0.703

Asia WGS AF: 0.760 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.81
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs741067; hg19: chr7-150500455;