dbSNP rs2306719: CA12:c.526-256A>G (chr15-63341039-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001218.5(CA12):c.526-256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,262 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.045 ( 198 hom., cov: 32)

Consequence

CA12
NM_001218.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700

Publications

9 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

CA12 links:

LOC124903506 (HGNC:):

LOC124903506 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-63341039-T-C is Benign according to our data. Variant chr15-63341039-T-C is described in ClinVar as [Benign]. Clinvar id is 1270897.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA12	NM_001218.5 link	c.526-256A>G		intron_variant	Intron 5 of 10	ENST00000178638.8	NP_001209.1	O43570-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CA12	ENST00000178638.8 link	c.526-256A>G	intron_variant	Intron 5 of 10	1	NM_001218.5	ENSP00000178638.3	O43570-1
CA12	ENST00000344366.7 link	c.526-256A>G	intron_variant	Intron 5 of 9	1		ENSP00000343088.3	O43570-2
CA12	ENST00000422263.2 link	c.346-256A>G	intron_variant	Intron 4 of 8	2		ENSP00000403028.2	B3KUB4
CA12	ENST00000558287.1 link	n.74-256A>G	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6803

AN:

152144

Hom.:

198

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0526

Gnomad ASJ

AF:

0.0809

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0510

Gnomad FIN

AF:

0.0497

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0626

Gnomad OTH

AF:

0.0508

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

GnomAD4 genome

AF:

0.0447

AC:

6806

AN:

152262

Hom.:

198

Cov.:

AF XY:

0.0440

AC XY:

3274

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0106

AC:

439

AN:

41558

American (AMR)

AF:

0.0525

AC:

804

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0809

AC:

281

AN:

3472

East Asian (EAS)

AF:

0.0133

AC:

AN:

5178

South Asian (SAS)

AF:

0.0516

AC:

249

AN:

4822

European-Finnish (FIN)

AF:

0.0497

AC:

527

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0626

AC:

4258

AN:

68014

Other (OTH)

AF:

0.0502

AC:

106

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

333

666

1000

1333

1666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0570

Hom.:

888

Bravo

AF:

0.0435

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

-0.0070

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over