chr15-63326051-G-A

Position:

• chr15-63326051-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001218.5(CA12):​c.*234C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 554,132 control chromosomes in the GnomAD database, including 1,029 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)
  • Exomes 𝑓: 0.058 (831 hom.)
• Consequence: CA12 NM_001218.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620

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]

LOC124903506 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-63326051-G-A is Benign according to our data. Variant chr15-63326051-G-A is described in ClinVar as [Benign]. Clinvar id is 1291975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA12	NM_001218.5	c.*234C>T		3_prime_UTR_variant	11/11	ENST00000178638.8
LOC124903506	XR_007064676.1	n.767+7297G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA12	ENST00000178638.8	c.*234C>T		3_prime_UTR_variant	11/11	1	NM_001218.5	A1
CA12	ENST00000344366.7	c.*234C>T		3_prime_UTR_variant	10/10	1		P4
CA12	ENST00000422263.2	c.*234C>T		3_prime_UTR_variant	9/9	2
CA12	ENST00000560666.1	n.509C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6821 AN: 152184 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0578 AC: 23229 AN: 401830 Hom.: 831 Cov.: 0 AF XY: 0.0588 AC XY: 12510 AN XY: 212654

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.0176

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.0586

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0576

GnomAD4 genome AF: 0.0448 AC: 6823 AN: 152302 Hom.: 198 Cov.: 32 AF XY: 0.0441 AC XY: 3284 AN XY: 74466

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0630

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0545 Hom.: 49

Bravo AF: 0.0435

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs11556746; hg19: chr15-63618250;