chr15-63338692-C-T

Position:

• chr15-63338692-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001218.5(CA12):​c.874+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,268,870 control chromosomes in the GnomAD database, including 2,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (200 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2120 hom.)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-63338692-C-T is Benign according to our data. Variant chr15-63338692-C-T is described in ClinVar as [Benign]. Clinvar id is 1282856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA12	NM_001218.5	c.874+127G>A		intron_variant		ENST00000178638.8	NP_001209.1
LOC124903506	XR_007064676.1	n.768-3122C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA12	ENST00000178638.8	c.874+127G>A		intron_variant		1	NM_001218.5	ENSP00000178638	A1
CA12	ENST00000344366.7	c.874+127G>A		intron_variant		1		ENSP00000343088	P4
CA12	ENST00000422263.2	c.694+127G>A		intron_variant		2		ENSP00000403028

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6794 AN: 152106 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0513

GnomAD4 exome AF: 0.0587 AC: 65592 AN: 1116646 Hom.: 2120 AF XY: 0.0596 AC XY: 33908 AN XY: 568522

Gnomad4 AFR exome AF: 0.00947

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0815

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.0597

Gnomad4 FIN exome AF: 0.0582

Gnomad4 NFE exome AF: 0.0628

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0447 AC: 6797 AN: 152224 Hom.: 200 Cov.: 32 AF XY: 0.0440 AC XY: 3271 AN XY: 74422

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0509

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0627

Gnomad4 OTH AF: 0.0508

Alfa AF: 0.0222 Hom.: 9

Bravo AF: 0.0434

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
CADD	Benign	0.45
DANN	Benign	0.84

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: rs12911704; hg19: chr15-63630891;