chr12-125346673-T-C

Variant names:

• chr12-125346673-T-C
• rs2197777
• NM_001366854.1:c.68-2779T>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.68-2779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,172 control chromosomes in the GnomAD database, including 6,953 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 0.30 (6953 hom., cov: 33)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366854.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	NM_001366854.1	MANE Select	c.68-2779T>C		intron	N/A	NP_001353783.1
	TMEM132B	NM_052907.3		c.53-2779T>C		intron	N/A	NP_443139.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	ENST00000682704.1	MANE Select	c.68-2779T>C		intron	N/A	ENSP00000507790.1
	TMEM132B	ENST00000299308.7	TSL:5	c.53-2779T>C		intron	N/A	ENSP00000299308.3
	TMEM132B	ENST00000535330.1	TSL:4	n.227-2779T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45229 AN: 152054 Hom.: 6948 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.297 AC: 45259 AN: 152172 Hom.: 6953 Cov.: 33 AF XY: 0.296 AC XY: 22015 AN XY: 74400

African (AFR) AF: 0.265 AC: 10998 AN: 41514

American (AMR) AF: 0.385 AC: 5887 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5176

South Asian (SAS) AF: 0.428 AC: 2066 AN: 4822

European-Finnish (FIN) AF: 0.203 AC: 2149 AN: 10594

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20682 AN: 67996

Other (OTH) AF: 0.295 AC: 623 AN: 2112

Alfa AF: 0.310 Hom.: 12098

Bravo AF: 0.307

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.82
PhyloP100		-1.8
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: rs2197777; hg19: chr12-125831219; COSMIC: COSV107339931; COSMIC: COSV107339931;