rs4984241

chr15-63331264-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001218.5(CA12):c.875-3134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,032 control chromosomes in the GnomAD database, including 22,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22211 hom., cov: 32)
• Consequence: CA12 NM_001218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA12	NM_001218.5	c.875-3134T>C		intron_variant		ENST00000178638.8
LOC124903506	XR_007064676.1	n.768-10550A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA12	ENST00000178638.8	c.875-3134T>C		intron_variant		1	NM_001218.5	A1
CA12	ENST00000344366.7	c.875-4031T>C		intron_variant		1		P4
CA12	ENST00000422263.2	c.695-4031T>C		intron_variant		2
CA12	ENST00000560666.1	n.117+433T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80516 AN: 151914 Hom.: 22205 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.530 AC: 80555 AN: 152032 Hom.: 22211 Cov.: 32 AF XY: 0.524 AC XY: 38901 AN XY: 74304

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.544

Alfa AF: 0.603 Hom.: 63560

Bravo AF: 0.523

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.4
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs4984241; hg19: chr15-63623463;