rs2306719

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
CA12NM_001218.5 linkuse as main transcriptc.526-256A>G intron_variant ENST00000178638.8
LOC124903506XR_007064676.1 linkuse as main transcriptn.768-775T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CA12ENST00000178638.8 linkuse as main transcriptc.526-256A>G intron_variant 1 NM_001218.5 A1O43570-1
CA12ENST00000344366.7 linkuse as main transcriptc.526-256A>G intron_variant 1 P4O43570-2
CA12ENST00000422263.2 linkuse as main transcriptc.346-256A>G intron_variant 2
CA12ENST00000558287.1 linkuse as main transcriptn.74-256A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0447
AC:
6803
AN:
152144
Hom.:
198
Cov.:
32
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.:
32
AF XY:
0.0440
AC XY:
3274
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0106
Gnomad4 AMR
AF:
0.0525
Gnomad4 ASJ
AF:
0.0809
Gnomad4 EAS
AF:
0.0133
Gnomad4 SAS
AF:
0.0516
Gnomad4 FIN
AF:
0.0497
Gnomad4 NFE
AF:
0.0626
Gnomad4 OTH
AF:
0.0502
Alfa
AF:
0.0614
Hom.:
437
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
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.8
DANN
Benign
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2306719; hg19: chr15-63633238; API