rs245914

Variant names:

• chr7-29178543-G-A
• rs245914
• NM_001371264.1:c.-11+2747C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-29178543-G-A
• chr7-29178543-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371264.1(CPVL):​c.-11+2747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 32)
• Consequence: CPVL NM_001371264.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPVL	NM_001371264.1	c.-11+2747C>T		intron_variant	Intron 4 of 15		NP_001358193.1
CPVL	NM_001348052.1	c.-11+2747C>T		intron_variant	Intron 3 of 14		NP_001334981.1
CPVL	NM_001348054.1	c.-11+2747C>T		intron_variant	Intron 2 of 13		NP_001334983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000409850.5	c.-11+2747C>T		intron_variant	Intron 5 of 16	2		ENSP00000387164.1
CPVL	ENST00000449801.5	c.-11+2747C>T		intron_variant	Intron 3 of 3	4		ENSP00000413287.1
CPVL	ENST00000455544.5	c.-11+2747C>T		intron_variant	Intron 4 of 4	4		ENSP00000412857.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151902 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151902 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74196

African (AFR) AF: 0.0000726 AC: 3 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 6667

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.66
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs245914; hg19: chr7-29218159;