NM_001218.5:c.908-268dupA

Variant names:

• chr15-63327500-G-GT
• rs74794784
• NM_001218.5:c.908-268dupA

Variant summary

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

The NM_001218.5(CA12):​c.908-268dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (6004 hom., cov: 0)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC124903506 (HGNC:):

ACMG classification

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

• BP6: Variant 15-63327500-G-GT is Benign according to our data. Variant chr15-63327500-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1278122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 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.908-268dupA		intron	N/A	NP_001209.1	O43570-1
	CA12	NM_206925.3		c.875-268dupA		intron	N/A	NP_996808.1	O43570-2
	CA12	NM_001293642.2		c.695-268dupA		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_908-267insA		intron	N/A	ENSP00000178638.3	O43570-1
	CA12	ENST00000344366.7	TSL:1	c.875-268_875-267insA		intron	N/A	ENSP00000343088.3	O43570-2
	CA12	ENST00000907869.1		c.902-268_902-267insA		intron	N/A	ENSP00000577928.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 41497 AN: 140226 Hom.: 6004 Cov.: 0

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.296 AC: 41500 AN: 140244 Hom.: 6004 Cov.: 0 AF XY: 0.293 AC XY: 19858 AN XY: 67810

African (AFR) AF: 0.277 AC: 10511 AN: 37900

American (AMR) AF: 0.399 AC: 5643 AN: 14130

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1176 AN: 3338

East Asian (EAS) AF: 0.186 AC: 893 AN: 4792

South Asian (SAS) AF: 0.280 AC: 1192 AN: 4254

European-Finnish (FIN) AF: 0.255 AC: 2167 AN: 8508

Middle Eastern (MID) AF: 0.255 AC: 70 AN: 274

European-Non Finnish (NFE) AF: 0.296 AC: 19063 AN: 64306

Other (OTH) AF: 0.330 AC: 619 AN: 1878

Alfa AF: 0.102 Hom.: 193

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		0.89
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

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;