15-63328338-CTTTT-CTTTTTTT

Variant names:

• chr15-63328338-C-CTTT
• rs57210378
• NM_001218.5:c.875-211_875-209dupAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001218.5(CA12):​c.875-211_875-209dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 140,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000036 (0 hom., cov: 24)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770

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]

LOC124903506 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA12	NM_001218.5	c.875-211_875-209dupAAA		intron_variant	Intron 8 of 10	ENST00000178638.8	NP_001209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA12	ENST00000178638.8	c.875-209_875-208insAAA		intron_variant	Intron 8 of 10	1	NM_001218.5	ENSP00000178638.3
CA12	ENST00000344366.7	c.875-1106_875-1105insAAA		intron_variant	Intron 8 of 9	1		ENSP00000343088.3
CA12	ENST00000422263.2	c.695-1106_695-1105insAAA		intron_variant	Intron 7 of 8	2		ENSP00000403028.2
CA12	ENST00000560666.1	n.118-1106_118-1105insAAA		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0000356 AC: 5 AN: 140408 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000709

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000356 AC: 5 AN: 140408 Hom.: 0 Cov.: 24 AF XY: 0.0000443 AC XY: 3 AN XY: 67678

Gnomad4 AFR AF: 0.000105

Gnomad4 AMR AF: 0.0000709

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57210378; hg19: chr15-63620537;