Genetic Variant NM_001366854.1:c.68-23040T>C (chr12-125326412-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

8 publications found

Variant links:

COSMIC-nc: COSV105161999

Genes affected

TMEM132B (HGNC:29397): (transmembrane protein 132B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM132B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001366854.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132B	NM_001366854.1	MANE Select	c.68-23040T>C		intron	N/A	NP_001353783.1	A0A804HK64
	TMEM132B	NM_052907.3		c.-212T>C		upstream_gene	N/A	NP_443139.2	Q14DG7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM132B	ENST00000682704.1	MANE Select	c.68-23040T>C	intron	N/A	ENSP00000507790.1	A0A804HK64
TMEM132B	ENST00000299308.7	TSL:5	c.-212T>C	upstream_gene	N/A	ENSP00000299308.3	Q14DG7-1
TMEM132B	ENST00000535330.1	TSL:4	n.-139T>C	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102374

AN:

151902

Hom.:

35251

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

4890

9781

14671

19562

24452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

958

1916

2874

3832

4790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.674

AC:

102481

AN:

152020

Hom.:

35301

Cov.:

AF XY:

0.685

AC XY:

50911

AN XY:

74322

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1664

3328

4992

6656

8320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.5

PromoterAI

0.019

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over