NM_001366854.1:c.68-23040T>C

Variant names:

• chr12-125326412-T-C
• rs551601
• NM_001366854.1:c.68-23040T>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.68-23040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 605,446 control chromosomes in the GnomAD database, including 128,240 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 0.67 (35301 hom., cov: 31)
  • Exomes 𝑓: 0.63 (92939 hom.)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.68-23040T>C		intron_variant	Intron 1 of 8	ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.68-23040T>C		intron_variant	Intron 1 of 8		NM_001366854.1	ENSP00000507790.1
TMEM132B	ENST00000299308.7	c.-212T>C		upstream_gene_variant		5		ENSP00000299308.3
TMEM132B	ENST00000535330.1	n.-139T>C		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102374 AN: 151902 Hom.: 35251 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.632 AC: 286625 AN: 453426 Hom.: 92939 AF XY: 0.637 AC XY: 152950 AN XY: 240058

African (AFR) AF: 0.796 AC: 10237 AN: 12864

American (AMR) AF: 0.742 AC: 18208 AN: 24546

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 9326 AN: 14418

East Asian (EAS) AF: 0.818 AC: 23459 AN: 28686

South Asian (SAS) AF: 0.745 AC: 36198 AN: 48604

European-Finnish (FIN) AF: 0.632 AC: 17526 AN: 27720

Middle Eastern (MID) AF: 0.619 AC: 1304 AN: 2108

European-Non Finnish (NFE) AF: 0.574 AC: 154219 AN: 268820

Other (OTH) AF: 0.629 AC: 16148 AN: 25660

GnomAD4 genome AF: 0.674 AC: 102481 AN: 152020 Hom.: 35301 Cov.: 31 AF XY: 0.685 AC XY: 50911 AN XY: 74322

African (AFR) AF: 0.794 AC: 32931 AN: 41458

American (AMR) AF: 0.720 AC: 11006 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3468

East Asian (EAS) AF: 0.812 AC: 4183 AN: 5154

South Asian (SAS) AF: 0.762 AC: 3658 AN: 4800

European-Finnish (FIN) AF: 0.665 AC: 7022 AN: 10552

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39298 AN: 67978

Other (OTH) AF: 0.675 AC: 1426 AN: 2114

Alfa AF: 0.615 Hom.: 99146

Bravo AF: 0.684

Asia WGS AF: 0.818 AC: 2843 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	14
DANN	Benign	0.67
PhyloP100		1.5
PromoterAI		0.019	Neutral

Splicing

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

Other links and lift over

dbSNP: rs551601; hg19: chr12-125810958; COSMIC: COSV105161999;