rs2306719

Positions:

• chr15-63341039-T-C

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

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=-0.84).
• 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
CA12	NM_001218.5	c.526-256A>G		intron_variant		ENST00000178638.8
LOC124903506	XR_007064676.1	n.768-775T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA12	ENST00000178638.8	c.526-256A>G		intron_variant		1	NM_001218.5	A1
CA12	ENST00000344366.7	c.526-256A>G		intron_variant		1		P4
CA12	ENST00000422263.2	c.346-256A>G		intron_variant		2
CA12	ENST00000558287.1	n.74-256A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6803 AN: 152144 Hom.: 198 Cov.: 32

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

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

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	-0.84
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

Other links and lift over

dbSNP: rs2306719; hg19: chr15-63633238;