rs10488012

Variant names:

• chr7-141318708-G-T
• rs10488012
• NM_001195278.2:c.496+106004G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001195278.2(TMEM178B):​c.496+106004G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,164 control chromosomes in the GnomAD database, including 1,710 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 0.13 (1710 hom., cov: 33)
• Consequence: TMEM178B NM_001195278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM178B	NM_001195278.2	c.496+106004G>T		intron_variant	Intron 2 of 3	ENST00000565468.6	NP_001182207.1
TMEM178B	XM_011515705.3	c.496+106004G>T		intron_variant	Intron 2 of 3		XP_011514007.1
TMEM178B	XM_017011636.2	c.496+106004G>T		intron_variant	Intron 2 of 3		XP_016867125.1
TMEM178B	XR_001744505.2	n.743+106004G>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM178B	ENST00000565468.6	c.496+106004G>T		intron_variant	Intron 2 of 3	5	NM_001195278.2	ENSP00000456594.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20358 AN: 152046 Hom.: 1710 Cov.: 33

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.134 AC: 20360 AN: 152164 Hom.: 1710 Cov.: 33 AF XY: 0.129 AC XY: 9626 AN XY: 74400

African (AFR) AF: 0.0511 AC: 2120 AN: 41518

American (AMR) AF: 0.137 AC: 2099 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5176

South Asian (SAS) AF: 0.0640 AC: 308 AN: 4812

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12724 AN: 68008

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.169 Hom.: 1386

Bravo AF: 0.129

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.69
PhyloP100		0.88
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: rs10488012; hg19: chr7-141018508;