Genetic Variant CPM:c.*1130T>C (chr12-68855307-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000551568.6(CPM):c.*1130T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,156 control chromosomes in the GnomAD database, including 3,092 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 0.19 ( 3084 hom., cov: 31)

Exomes 𝑓: 0.21 ( 8 hom. )

Consequence

CPM
ENST00000551568.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551568.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPM	NM_198320.5	MANE Select	c.*1130T>C	3_prime_UTR	Exon 9 of 9	NP_938079.1
CPM	NR_182143.1		n.3226T>C	non_coding_transcript_exon	Exon 10 of 10
CPM	NM_001413387.1		c.*1130T>C	3_prime_UTR	Exon 9 of 9	NP_001400316.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPM	ENST00000551568.6	TSL:1 MANE Select	c.*1130T>C	3_prime_UTR	Exon 9 of 9	ENSP00000448517.1
CPM	ENST00000338356.7	TSL:1	c.*1130T>C	3_prime_UTR	Exon 8 of 8	ENSP00000339157.3
CPM	ENST00000551897.5	TSL:5	c.531+1337T>C	intron	N/A	ENSP00000447455.1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29542

AN:

151892

Hom.:

3080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.212

AC:

AN:

146

Hom.:

Cov.:

AF XY:

0.219

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0556

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.269

AC:

AN:

104

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.195

AC:

29573

AN:

152010

Hom.:

3084

Cov.:

AF XY:

0.191

AC XY:

14165

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.179

AC:

7418

AN:

41482

American (AMR)

AF:

0.177

AC:

2706

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

758

AN:

3466

East Asian (EAS)

AF:

0.0102

AC:

AN:

5174

South Asian (SAS)

AF:

0.135

AC:

647

AN:

4792

European-Finnish (FIN)

AF:

0.172

AC:

1813

AN:

10560

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15333

AN:

67944

Other (OTH)

AF:

0.229

AC:

484

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1203

2406

3608

4811

6014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.213

Hom.:

1808

Bravo

AF:

0.195

Asia WGS

AF:

0.0690

AC:

239

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.40

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over