12-125197215-C-T

Variant names:

• chr12-125197215-C-T
• rs12578774
• NM_001366854.1:c.67+10349C>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.67+10349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,966 control chromosomes in the GnomAD database, including 5,335 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 0.25 (5335 hom., cov: 32)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.67+10349C>T		intron_variant	Intron 1 of 8	ENST00000682704.1	NP_001353783.1
TMEM132B	XM_047428245.1	c.67+10349C>T		intron_variant	Intron 1 of 4		XP_047284201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.67+10349C>T		intron_variant	Intron 1 of 8		NM_001366854.1	ENSP00000507790.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38449 AN: 151848 Hom.: 5321 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.253 AC: 38492 AN: 151966 Hom.: 5335 Cov.: 32 AF XY: 0.256 AC XY: 19007 AN XY: 74260

African (AFR) AF: 0.156 AC: 6450 AN: 41450

American (AMR) AF: 0.261 AC: 3983 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2423 AN: 5144

South Asian (SAS) AF: 0.295 AC: 1415 AN: 4802

European-Finnish (FIN) AF: 0.287 AC: 3023 AN: 10528

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19723 AN: 67984

Other (OTH) AF: 0.235 AC: 495 AN: 2110

Alfa AF: 0.265 Hom.: 14658

Bravo AF: 0.244

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.57
PhyloP100		-0.099

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12578774; hg19: chr12-125681761;