12-125326510-A-G

Variant names:

• chr12-125326510-A-G
• rs550677
• NM_001366854.1:c.68-22942A>G

Variant summary

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

The NM_001366854.1(TMEM132B):​c.68-22942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 1,218,646 control chromosomes in the GnomAD database, including 240,656 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 0.68 (36008 hom., cov: 23)
  • Exomes 𝑓: 0.61 (204648 hom.)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 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.68-22942A>G		intron	N/A	NP_001353783.1
	TMEM132B	NM_052907.3		c.-114A>G		upstream_gene	N/A	NP_443139.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	ENST00000682704.1	MANE Select	c.68-22942A>G		intron	N/A	ENSP00000507790.1
	TMEM132B	ENST00000299308.7	TSL:5	c.-114A>G		upstream_gene	N/A	ENSP00000299308.3
	TMEM132B	ENST00000535330.1	TSL:4	n.-41A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.684 AC: 102508 AN: 149956 Hom.: 35951 Cov.: 23

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.681

GnomAD4 exome AF: 0.611 AC: 653363 AN: 1068572 Hom.: 204648 Cov.: 14 AF XY: 0.614 AC XY: 332795 AN XY: 541600

African (AFR) AF: 0.839 AC: 21421 AN: 25524

American (AMR) AF: 0.744 AC: 26065 AN: 35052

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 14955 AN: 22966

East Asian (EAS) AF: 0.819 AC: 28203 AN: 34424

South Asian (SAS) AF: 0.743 AC: 53633 AN: 72190

European-Finnish (FIN) AF: 0.640 AC: 28701 AN: 44860

Middle Eastern (MID) AF: 0.646 AC: 3234 AN: 5008

European-Non Finnish (NFE) AF: 0.572 AC: 447274 AN: 781588

Other (OTH) AF: 0.636 AC: 29877 AN: 46960

GnomAD4 genome AF: 0.684 AC: 102621 AN: 150074 Hom.: 36008 Cov.: 23 AF XY: 0.695 AC XY: 50791 AN XY: 73116

African (AFR) AF: 0.829 AC: 33717 AN: 40692

American (AMR) AF: 0.724 AC: 10962 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2224 AN: 3454

East Asian (EAS) AF: 0.810 AC: 4062 AN: 5012

South Asian (SAS) AF: 0.762 AC: 3543 AN: 4648

European-Finnish (FIN) AF: 0.668 AC: 6857 AN: 10272

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39110 AN: 67582

Other (OTH) AF: 0.683 AC: 1427 AN: 2088

Alfa AF: 0.623 Hom.: 46091

Bravo AF: 0.695

Asia WGS AF: 0.822 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		0.16
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs550677; hg19: chr12-125811056;