chr7-141113257-C-T

Variant names:

• chr7-141113257-C-T
• rs4725500
• NM_001195278.2:c.382+38565C>T

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+38565C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,058 control chromosomes in the GnomAD database, including 9,723 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 0.32 (9723 hom., cov: 32)
• Consequence: TMEM178B NM_001195278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM178B	NM_001195278.2	c.382+38565C>T		intron_variant	Intron 1 of 3	ENST00000565468.6	NP_001182207.1
TMEM178B	XM_011515705.3	c.382+38565C>T		intron_variant	Intron 1 of 3		XP_011514007.1
TMEM178B	XM_017011636.2	c.382+38565C>T		intron_variant	Intron 1 of 3		XP_016867125.1
TMEM178B	XR_001744505.2	n.629+38565C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM178B	ENST00000565468.6	c.382+38565C>T		intron_variant	Intron 1 of 3	5	NM_001195278.2	ENSP00000456594.1
TMEM178B	ENST00000563442.1	n.300+38565C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48477 AN: 151940 Hom.: 9728 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.319 AC: 48470 AN: 152058 Hom.: 9723 Cov.: 32 AF XY: 0.312 AC XY: 23193 AN XY: 74314

African (AFR) AF: 0.0933 AC: 3873 AN: 41520

American (AMR) AF: 0.349 AC: 5326 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3472

East Asian (EAS) AF: 0.160 AC: 823 AN: 5156

South Asian (SAS) AF: 0.193 AC: 929 AN: 4806

European-Finnish (FIN) AF: 0.374 AC: 3944 AN: 10558

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.458 AC: 31143 AN: 67950

Other (OTH) AF: 0.353 AC: 747 AN: 2116

Alfa AF: 0.291 Hom.: 3494

Bravo AF: 0.309

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.76
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4725500; hg19: chr7-140813057;