rs2306719

Variant names:

• chr15-63341039-T-C
• rs2306719
• NM_001218.5:c.526-256A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

CA12 Gene-Disease associations (from GenCC):

• isolated hyperchlorhidrosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

LOC124903506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001218.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA12	NM_001218.5	MANE Select	c.526-256A>G		intron	N/A	NP_001209.1	O43570-1
	CA12	NM_206925.3		c.526-256A>G		intron	N/A	NP_996808.1	O43570-2
	CA12	NM_001293642.2		c.346-256A>G		intron	N/A	NP_001280571.1	B3KUB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA12	ENST00000178638.8	TSL:1 MANE Select	c.526-256A>G		intron	N/A	ENSP00000178638.3	O43570-1
	CA12	ENST00000344366.7	TSL:1	c.526-256A>G		intron	N/A	ENSP00000343088.3	O43570-2
	CA12	ENST00000907869.1		c.526-256A>G		intron	N/A	ENSP00000577928.1

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

African (AFR) AF: 0.0106 AC: 439 AN: 41558

American (AMR) AF: 0.0525 AC: 804 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5178

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4822

European-Finnish (FIN) AF: 0.0497 AC: 527 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4258 AN: 68014

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0570 Hom.: 888

Bravo AF: 0.0435

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2306719;

hg19: chr15-63633238;