15-63327500-GTTTTTT-GTTTTTTTTT

Variant names:

• chr15-63327500-G-GTTT
• rs74794784
• NM_001218.5:c.908-270_908-268dupAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001218.5(CA12):​c.908-270_908-268dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0027 (1 hom., cov: 0)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

LOC124903506 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00274 (385/140338) while in subpopulation SAS AF = 0.0402 (171/4256). AF 95% confidence interval is 0.0353. There are 1 homozygotes in GnomAd4. There are 225 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.908-270_908-268dupAAA		intron	N/A	NP_001209.1	O43570-1
	CA12	NM_206925.3		c.875-270_875-268dupAAA		intron	N/A	NP_996808.1	O43570-2
	CA12	NM_001293642.2		c.695-270_695-268dupAAA		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.908-268_908-267insAAA		intron	N/A	ENSP00000178638.3	O43570-1
	CA12	ENST00000344366.7	TSL:1	c.875-268_875-267insAAA		intron	N/A	ENSP00000343088.3	O43570-2
	CA12	ENST00000907869.1		c.902-268_902-267insAAA		intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 386 AN: 140322 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000637

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00125

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.000117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000777

Gnomad OTH AF: 0.00213

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

GnomAD4 genome AF: 0.00274 AC: 385 AN: 140338 Hom.: 1 Cov.: 0 AF XY: 0.00332 AC XY: 225 AN XY: 67852

African (AFR) AF: 0.00499 AC: 189 AN: 37910

American (AMR) AF: 0.000636 AC: 9 AN: 14148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.00125 AC: 6 AN: 4792

South Asian (SAS) AF: 0.0402 AC: 171 AN: 4256

European-Finnish (FIN) AF: 0.000117 AC: 1 AN: 8532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.0000777 AC: 5 AN: 64340

Other (OTH) AF: 0.00213 AC: 4 AN: 1880

Alfa AF: 0.00 Hom.: 193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism

Splicing

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: rs74794784;

hg19: chr15-63619699;