rs2694874

Variant names:

• chr12-125517918-G-C
• rs2694874
• NM_001366854.1:c.1107-1521G>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.1107-1521G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,046 control chromosomes in the GnomAD database, including 18,420 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 0.45 (18420 hom., cov: 32)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.1107-1521G>C		intron_variant	Intron 3 of 8	ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.1107-1521G>C		intron_variant	Intron 3 of 8		NM_001366854.1	ENSP00000507790.1
TMEM132B	ENST00000299308.7	c.1092-1521G>C		intron_variant	Intron 3 of 8	5		ENSP00000299308.3
TMEM132B	ENST00000534945.2	n.1040-1521G>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68226 AN: 151928 Hom.: 18359 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.450 AC: 68356 AN: 152046 Hom.: 18420 Cov.: 32 AF XY: 0.458 AC XY: 34015 AN XY: 74332

African (AFR) AF: 0.697 AC: 28907 AN: 41466

American (AMR) AF: 0.519 AC: 7921 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1184 AN: 3468

East Asian (EAS) AF: 0.850 AC: 4391 AN: 5166

South Asian (SAS) AF: 0.491 AC: 2369 AN: 4820

European-Finnish (FIN) AF: 0.344 AC: 3630 AN: 10560

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18765 AN: 67976

Other (OTH) AF: 0.414 AC: 874 AN: 2112

Alfa AF: 0.374 Hom.: 1568

Bravo AF: 0.476

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		-0.049
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2694874; hg19: chr12-126002464;