chr15-63339269-A-AT

Position:

• chr15-63339269-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001218.5(CA12):​c.748-325_748-324insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 140,716 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.048 (197 hom., cov: 32)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

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 -10 ACMG points.

• BP6: Variant 15-63339269-A-AT is Benign according to our data. Variant chr15-63339269-A-AT is described in ClinVar as [Benign]. Clinvar id is 1291991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA12	NM_001218.5	c.748-325_748-324insA		intron_variant		ENST00000178638.8
LOC124903506	XR_007064676.1	n.768-2545_768-2544insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA12	ENST00000178638.8	c.748-325_748-324insA		intron_variant		1	NM_001218.5	A1
CA12	ENST00000344366.7	c.748-325_748-324insA		intron_variant		1		P4
CA12	ENST00000422263.2	c.568-325_568-324insA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 6782 AN: 140602 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0631

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.0690

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0553

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

GnomAD4 genome AF: 0.0482 AC: 6785 AN: 140716 Hom.: 197 Cov.: 32 AF XY: 0.0477 AC XY: 3263 AN XY: 68448

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0144

Gnomad4 SAS AF: 0.0575

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0546

Alfa AF: 0.0482 Hom.: 24

Asia WGS AF: 0.0360 AC: 126 AN: 3472

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

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: rs35810559; hg19: chr15-63631468;