chr12-125520506-T-C

Position:

• chr12-125520506-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.1293+881T>C		intron_variant		ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.1293+881T>C		intron_variant			NM_001366854.1	ENSP00000507790	P2
TMEM132B	ENST00000299308.7	c.1278+881T>C		intron_variant		5		ENSP00000299308	A2
TMEM132B	ENST00000534945.2	n.1226+881T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.433

Alfa AF: 0.485 Hom.: 2601

Bravo AF: 0.489

Asia WGS AF: 0.502 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs866435; hg19: chr12-126005052;