12-125520506-T-C

Variant names:

• chr12-125520506-T-C
• rs866435
• NM_001366854.1:c.1293+881T>C

Variant summary

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

The NM_001366854.1(TMEM132B):​c.1293+881T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,784 control chromosomes in the GnomAD database, including 18,010 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 0.48 (18010 hom., cov: 31)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 1 publications found

Genes affected

TMEM132B (HGNC:29397): (transmembrane protein 132B) 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366854.1. 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
	TMEM132B	NM_001366854.1	MANE Select	c.1293+881T>C		intron	N/A	NP_001353783.1
	TMEM132B	NM_052907.3		c.1278+881T>C		intron	N/A	NP_443139.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	ENST00000682704.1	MANE Select	c.1293+881T>C		intron	N/A	ENSP00000507790.1
	TMEM132B	ENST00000299308.7	TSL:5	c.1278+881T>C		intron	N/A	ENSP00000299308.3
	TMEM132B	ENST00000534945.2	TSL:5	n.1226+881T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73426 AN: 151668 Hom.: 17985 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.484 AC: 73511 AN: 151784 Hom.: 18010 Cov.: 31 AF XY: 0.483 AC XY: 35844 AN XY: 74154

African (AFR) AF: 0.560 AC: 23147 AN: 41346

American (AMR) AF: 0.458 AC: 6996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1483 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3032 AN: 5138

South Asian (SAS) AF: 0.462 AC: 2216 AN: 4792

European-Finnish (FIN) AF: 0.469 AC: 4931 AN: 10516

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.448 AC: 30445 AN: 67952

Other (OTH) AF: 0.433 AC: 909 AN: 2100

Alfa AF: 0.487 Hom.: 2721

Bravo AF: 0.489

Asia WGS AF: 0.502 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.26
PhyloP100		0.066
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: rs866435; hg19: chr12-126005052;