rs12700939

Positions:

• chr7-29153130-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPVL	NM_001348052.1	c.-11+28160T>C		intron_variant			NP_001334981.1
CPVL	NM_001348054.1	c.-11+28160T>C		intron_variant			NP_001334983.1
CPVL	NM_001371255.1	c.-11+20568T>C		intron_variant			NP_001358184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000409850.5	c.-11+28160T>C		intron_variant		2		ENSP00000387164	P1
CPVL	ENST00000437527.1	c.-11+28160T>C		intron_variant		4		ENSP00000416555
CPVL	ENST00000449801.5	c.-11+28160T>C		intron_variant		4		ENSP00000413287

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

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.358

Alfa AF: 0.354 Hom.: 2530

Bravo AF: 0.326

Asia WGS AF: 0.312 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12700939; hg19: chr7-29192746;