12-125558577-C-T

Variant names:

• chr12-125558577-C-T
• rs10846917
• NM_001366854.1:c.1294-25274C>T

Variant summary

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

The NM_001366854.1(TMEM132B):​c.1294-25274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,024 control chromosomes in the GnomAD database, including 26,486 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 0.57 (26486 hom., cov: 32)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.1294-25274C>T		intron_variant	Intron 4 of 8	ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.1294-25274C>T		intron_variant	Intron 4 of 8		NM_001366854.1	ENSP00000507790.1
TMEM132B	ENST00000299308.7	c.1279-25274C>T		intron_variant	Intron 4 of 8	5		ENSP00000299308.3
TMEM132B	ENST00000534945.2	n.1227-25274C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86652 AN: 151906 Hom.: 26483 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.570 AC: 86665 AN: 152024 Hom.: 26486 Cov.: 32 AF XY: 0.569 AC XY: 42291 AN XY: 74288

African (AFR) AF: 0.344 AC: 14272 AN: 41460

American (AMR) AF: 0.594 AC: 9064 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2564 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1890 AN: 5160

South Asian (SAS) AF: 0.574 AC: 2768 AN: 4820

European-Finnish (FIN) AF: 0.670 AC: 7079 AN: 10558

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46821 AN: 67970

Other (OTH) AF: 0.610 AC: 1287 AN: 2110

Alfa AF: 0.621 Hom.: 6508

Bravo AF: 0.551

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.66
PhyloP100		-0.91
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: rs10846917; hg19: chr12-126043123;