7-141079940-T-C

Variant names:

• chr7-141079940-T-C
• rs557962
• NM_001195278.2:c.382+5248T>C

Variant summary

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

The NM_001195278.2(TMEM178B):​c.382+5248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,278 control chromosomes in the GnomAD database, including 64,155 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 0.92 (64155 hom., cov: 32)
• Consequence: TMEM178B NM_001195278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178B	NM_001195278.2	MANE Select	c.382+5248T>C		intron	N/A	NP_001182207.1	H3BS89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM178B	ENST00000565468.6	TSL:5 MANE Select	c.382+5248T>C		intron	N/A	ENSP00000456594.1	H3BS89
	TMEM178B	ENST00000563442.1	TSL:2	n.300+5248T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139601 AN: 152160 Hom.: 64095 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.918 AC: 139719 AN: 152278 Hom.: 64155 Cov.: 32 AF XY: 0.917 AC XY: 68255 AN XY: 74440

African (AFR) AF: 0.940 AC: 39027 AN: 41540

American (AMR) AF: 0.924 AC: 14128 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3008 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4666 AN: 5186

South Asian (SAS) AF: 0.856 AC: 4126 AN: 4822

European-Finnish (FIN) AF: 0.937 AC: 9941 AN: 10604

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61758 AN: 68036

Other (OTH) AF: 0.918 AC: 1940 AN: 2114

Alfa AF: 0.907 Hom.: 98677

Bravo AF: 0.919

Asia WGS AF: 0.897 AC: 3118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-0.044
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: rs557962; hg19: chr7-140779740;