rs12700939

Variant names:

• chr7-29153130-A-G
• rs12700939
• NM_001371264.1:c.-11+28160T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371264.1(CPVL):​c.-11+28160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,078 control chromosomes in the GnomAD database, including 8,844 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 0.34 (8844 hom., cov: 33)
• Consequence: CPVL NM_001371264.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 12 publications found

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371264.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	NM_001371264.1		c.-11+28160T>C		intron	N/A	NP_001358193.1
	CPVL	NM_001348052.1		c.-11+28160T>C		intron	N/A	NP_001334981.1
	CPVL	NM_001348054.1		c.-11+28160T>C		intron	N/A	NP_001334983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	ENST00000409850.5	TSL:2	c.-11+28160T>C		intron	N/A	ENSP00000387164.1
	CPVL	ENST00000449801.5	TSL:4	c.-11+28160T>C		intron	N/A	ENSP00000413287.1
	CPVL	ENST00000455544.5	TSL:4	c.-11+28160T>C		intron	N/A	ENSP00000412857.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51124 AN: 151960 Hom.: 8837 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.336 AC: 51141 AN: 152078 Hom.: 8844 Cov.: 33 AF XY: 0.334 AC XY: 24860 AN XY: 74336

African (AFR) AF: 0.253 AC: 10484 AN: 41500

American (AMR) AF: 0.298 AC: 4550 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1786 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4812

European-Finnish (FIN) AF: 0.405 AC: 4275 AN: 10552

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25895 AN: 67980

Other (OTH) AF: 0.358 AC: 756 AN: 2112

Alfa AF: 0.355 Hom.: 3966

Bravo AF: 0.326

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.92
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12700939; hg19: chr7-29192746;