rs2694874

chr12-125517918-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TMEM132B	NM_001366854.1	c.1107-1521G>C		intron_variant		ENST00000682704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132B	ENST00000682704.1	c.1107-1521G>C		intron_variant			NM_001366854.1	P2
TMEM132B	ENST00000299308.7	c.1092-1521G>C		intron_variant		5		A2
TMEM132B	ENST00000534945.2	n.1040-1521G>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.414

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2694874; hg19: chr12-126002464;