NM_001218.5:c.875-3134T>C

Variant names:

• chr15-63331264-A-G
• rs4984241
• NM_001218.5:c.875-3134T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001218.5(CA12):​c.875-3134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,032 control chromosomes in the GnomAD database, including 22,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22211 hom., cov: 32)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 15 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), Orphanet, Ambry Genetics

LOC124903506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA12	NM_001218.5	MANE Select	c.875-3134T>C		intron	N/A	NP_001209.1
	CA12	NM_206925.3		c.875-4031T>C		intron	N/A	NP_996808.1
	CA12	NM_001293642.2		c.695-4031T>C		intron	N/A	NP_001280571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA12	ENST00000178638.8	TSL:1 MANE Select	c.875-3134T>C		intron	N/A	ENSP00000178638.3
	CA12	ENST00000344366.7	TSL:1	c.875-4031T>C		intron	N/A	ENSP00000343088.3
	CA12	ENST00000907869.1		c.875-3140T>C		intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80516 AN: 151914 Hom.: 22205 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.530 AC: 80555 AN: 152032 Hom.: 22211 Cov.: 32 AF XY: 0.524 AC XY: 38901 AN XY: 74304

African (AFR) AF: 0.401 AC: 16616 AN: 41460

American (AMR) AF: 0.501 AC: 7647 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2073 AN: 5162

South Asian (SAS) AF: 0.422 AC: 2036 AN: 4822

European-Finnish (FIN) AF: 0.554 AC: 5850 AN: 10566

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42432 AN: 67964

Other (OTH) AF: 0.544 AC: 1147 AN: 2108

Alfa AF: 0.593 Hom.: 127279

Bravo AF: 0.523

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.52
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4984241; hg19: chr15-63623463;