Genetic Variant CA12:c.875-209delA (chr15-63328338-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001218.5(CA12):c.875-209delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 140,272 control chromosomes in the GnomAD database, including 262 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.072 ( 262 hom., cov: 24)

Consequence

CA12
NM_001218.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.770

Publications

0 publications found

Variant links:

Genes affected

CA12 (HGNC:1371): (carbonic anhydrase 12) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]

CA12 Gene-Disease associations (from GenCC):

isolated hyperchlorhidrosis
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

CA12 links:

LOC124903506 (HGNC:):

LOC124903506 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-63328338-CT-C is Benign according to our data. Variant chr15-63328338-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1245197.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001218.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CA12	NM_001218.5	MANE Select	c.875-209delA	intron	N/A	NP_001209.1	O43570-1
CA12	NM_206925.3		c.875-1106delA	intron	N/A	NP_996808.1	O43570-2
CA12	NM_001293642.2		c.695-1106delA	intron	N/A	NP_001280571.1	B3KUB4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CA12	ENST00000178638.8	TSL:1 MANE Select	c.875-209delA	intron	N/A	ENSP00000178638.3	O43570-1
CA12	ENST00000344366.7	TSL:1	c.875-1106delA	intron	N/A	ENSP00000343088.3	O43570-2
CA12	ENST00000907869.1		c.875-215delA	intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes

AF:

0.0723

AC:

10143

AN:

140258

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0764

Gnomad AMI

AF:

0.0609

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0130

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0925

Gnomad NFE

AF:

0.0758

Gnomad OTH

AF:

0.0757

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0724

AC:

10152

AN:

140272

Hom.:

262

Cov.:

AF XY:

0.0706

AC XY:

4773

AN XY:

67650

show subpopulations

African (AFR)

AF:

0.0765

AC:

2922

AN:

38184

American (AMR)

AF:

0.0705

AC:

995

AN:

14110

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

335

AN:

3346

East Asian (EAS)

AF:

0.0128

AC:

AN:

4754

South Asian (SAS)

AF:

0.0595

AC:

257

AN:

4322

European-Finnish (FIN)

AF:

0.0587

AC:

476

AN:

8112

Middle Eastern (MID)

AF:

0.0940

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0758

AC:

4884

AN:

64398

Other (OTH)

AF:

0.0755

AC:

143

AN:

1894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

373

747

1120

1494

1867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0117

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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15-63328338-CTTTT-CTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over