15-63328338-CTTTT-CTTTTT

Variant names:

• chr15-63328338-C-CT
• rs57210378
• NM_001218.5:c.875-209dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001218.5(CA12):​c.875-209dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 140,366 control chromosomes in the GnomAD database, including 1,790 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1790 hom., cov: 24)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.770
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC124903506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-63328338-C-CT is Benign according to our data. Variant chr15-63328338-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1263601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 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.875-209dupA		intron	N/A	NP_001209.1	O43570-1
	CA12	NM_206925.3		c.875-1106dupA		intron	N/A	NP_996808.1	O43570-2
	CA12	NM_001293642.2		c.695-1106dupA		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.875-209_875-208insA		intron	N/A	ENSP00000178638.3	O43570-1
	CA12	ENST00000344366.7	TSL:1	c.875-1106_875-1105insA		intron	N/A	ENSP00000343088.3	O43570-2
	CA12	ENST00000907869.1		c.875-215_875-214insA		intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 19860 AN: 140352 Hom.: 1790 Cov.: 24

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.142 AC: 19866 AN: 140366 Hom.: 1790 Cov.: 24 AF XY: 0.148 AC XY: 10021 AN XY: 67670

African (AFR) AF: 0.129 AC: 4911 AN: 38194

American (AMR) AF: 0.175 AC: 2468 AN: 14110

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 493 AN: 3352

East Asian (EAS) AF: 0.458 AC: 2175 AN: 4752

South Asian (SAS) AF: 0.284 AC: 1226 AN: 4322

European-Finnish (FIN) AF: 0.158 AC: 1286 AN: 8140

Middle Eastern (MID) AF: 0.135 AC: 36 AN: 266

European-Non Finnish (NFE) AF: 0.107 AC: 6884 AN: 64450

Other (OTH) AF: 0.140 AC: 266 AN: 1894

Alfa AF: 0.0313 Hom.: 29

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
PhyloP100		0.77
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: rs57210378; hg19: chr15-63620537; COSMIC: COSV107193298;