15-63328338-CTTTT-CTTTTTT

Variant names:

• chr15-63328338-C-CTT
• rs57210378
• NM_001218.5:c.875-210_875-209dupAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001218.5(CA12):​c.875-210_875-209dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 140,396 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0055 (8 hom., cov: 24)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.875-210_875-209dupAA		intron	N/A	NP_001209.1	O43570-1
	CA12	NM_206925.3		c.875-1107_875-1106dupAA		intron	N/A	NP_996808.1	O43570-2
	CA12	NM_001293642.2		c.695-1107_695-1106dupAA		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_875-208insAA		intron	N/A	ENSP00000178638.3	O43570-1
	CA12	ENST00000344366.7	TSL:1	c.875-1106_875-1105insAA		intron	N/A	ENSP00000343088.3	O43570-2
	CA12	ENST00000907869.1		c.875-215_875-214insAA		intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 773 AN: 140382 Hom.: 9 Cov.: 24

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00348

Gnomad ASJ AF: 0.000596

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000248

Gnomad OTH AF: 0.00476

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

GnomAD4 genome AF: 0.00550 AC: 772 AN: 140396 Hom.: 8 Cov.: 24 AF XY: 0.00570 AC XY: 386 AN XY: 67704

African (AFR) AF: 0.0157 AC: 600 AN: 38198

American (AMR) AF: 0.00347 AC: 49 AN: 14112

Ashkenazi Jewish (ASJ) AF: 0.000596 AC: 2 AN: 3354

East Asian (EAS) AF: 0.0147 AC: 70 AN: 4754

South Asian (SAS) AF: 0.00416 AC: 18 AN: 4324

European-Finnish (FIN) AF: 0.000983 AC: 8 AN: 8140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.000248 AC: 16 AN: 64466

Other (OTH) AF: 0.00475 AC: 9 AN: 1896

Alfa AF: 0.00 Hom.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57210378; hg19: chr15-63620537;