dbSNP rs3741599: CPM:c.1090-22A>G (chr12-68856701-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_198320.5(CPM):c.1090-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,609,374 control chromosomes in the GnomAD database, including 30,277 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.17 ( 2423 hom., cov: 33)

Exomes 𝑓: 0.19 ( 27854 hom. )

Consequence

CPM
NM_198320.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217

Publications

9 publications found

Variant links:

Genes affected

CPM (HGNC:2311): (carboxypeptidase M) The protein encoded by this gene is a membrane-bound arginine/lysine carboxypeptidase. Its expression is associated with monocyte to macrophage differentiation. This encoded protein contains hydrophobic regions at the amino and carboxy termini and has 6 potential asparagine-linked glycosylation sites. The active site residues of carboxypeptidases A and B are conserved in this protein. Three alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

CPM links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPM	NM_198320.5 link	c.1090-22A>G		intron_variant	Intron 8 of 8	ENST00000551568.6	NP_938079.1	P14384

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6 link	c.1090-22A>G		intron_variant	Intron 8 of 8	1	NM_198320.5	ENSP00000448517.1		P14384

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25706

AN:

152038

Hom.:

2419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.169

AC:

41938

AN:

248842

AF XY:

0.172

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.191

AC:

277833

AN:

1457218

Hom.:

27854

Cov.:

AF XY:

0.191

AC XY:

138153

AN XY:

724492

show subpopulations

African (AFR)

AF:

0.112

AC:

3734

AN:

33290

American (AMR)

AF:

0.165

AC:

7326

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5555

AN:

25914

East Asian (EAS)

AF:

0.0113

AC:

447

AN:

39634

South Asian (SAS)

AF:

0.153

AC:

13152

AN:

85990

European-Finnish (FIN)

AF:

0.159

AC:

8465

AN:

53310

Middle Eastern (MID)

AF:

0.263

AC:

1511

AN:

5740

European-Non Finnish (NFE)

AF:

0.204

AC:

226511

AN:

1108884

Other (OTH)

AF:

0.185

AC:

11132

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10624

21247

31871

42494

53118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7656

15312

22968

30624

38280

<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:

0.169

AC:

25725

AN:

152156

Hom.:

2423

Cov.:

AF XY:

0.166

AC XY:

12381

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.117

AC:

4872

AN:

41520

American (AMR)

AF:

0.194

AC:

2960

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

716

AN:

3472

East Asian (EAS)

AF:

0.0108

AC:

AN:

5186

South Asian (SAS)

AF:

0.140

AC:

674

AN:

4820

European-Finnish (FIN)

AF:

0.151

AC:

1601

AN:

10582

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14056

AN:

67990

Other (OTH)

AF:

0.208

AC:

439

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1093

2185

3278

4370

5463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.189

Hom.:

1590

Bravo

AF:

0.170

Asia WGS

AF:

0.0670

AC:

231

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.22

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over