rs10215677

Variant names:

• chr7-141385714-A-G
• rs10215677
• NM_001195278.2:c.497-51894A>G

Variant summary

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

The NM_001195278.2(TMEM178B):​c.497-51894A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,064 control chromosomes in the GnomAD database, including 6,552 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 0.28 (6552 hom., cov: 32)
• Consequence: TMEM178B NM_001195278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 3 publications found

Genes affected

TMEM178B (HGNC:44112): (transmembrane protein 178B) Predicted to be integral component of membrane. Predicted to be active in 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195278.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178B	NM_001195278.2	MANE Select	c.497-51894A>G		intron	N/A	NP_001182207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178B	ENST00000565468.6	TSL:5 MANE Select	c.497-51894A>G		intron	N/A	ENSP00000456594.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42748 AN: 151950 Hom.: 6530 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.282 AC: 42838 AN: 152064 Hom.: 6552 Cov.: 32 AF XY: 0.278 AC XY: 20679 AN XY: 74326

African (AFR) AF: 0.385 AC: 15969 AN: 41434

American (AMR) AF: 0.292 AC: 4472 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3466

East Asian (EAS) AF: 0.0589 AC: 305 AN: 5180

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10580

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16923 AN: 67974

Other (OTH) AF: 0.289 AC: 612 AN: 2114

Alfa AF: 0.261 Hom.: 9819

Bravo AF: 0.291

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.52
PhyloP100		0.41
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: rs10215677; hg19: chr7-141085514;