7-29178543-G-T

Variant names:

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

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+2747C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,976 control chromosomes in the GnomAD database, including 2,203 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 0.17 (2203 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 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+2747C>A		intron	N/A	NP_001358193.1
	CPVL	NM_001348052.1		c.-11+2747C>A		intron	N/A	NP_001334981.1
	CPVL	NM_001348054.1		c.-11+2747C>A		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+2747C>A		intron	N/A	ENSP00000387164.1
	CPVL	ENST00000449801.5	TSL:4	c.-11+2747C>A		intron	N/A	ENSP00000413287.1
	CPVL	ENST00000455544.5	TSL:4	c.-11+2747C>A		intron	N/A	ENSP00000412857.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25583 AN: 151858 Hom.: 2203 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.168 AC: 25593 AN: 151976 Hom.: 2203 Cov.: 32 AF XY: 0.167 AC XY: 12424 AN XY: 74294

African (AFR) AF: 0.189 AC: 7836 AN: 41430

American (AMR) AF: 0.168 AC: 2559 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3466

East Asian (EAS) AF: 0.116 AC: 599 AN: 5156

South Asian (SAS) AF: 0.143 AC: 685 AN: 4788

European-Finnish (FIN) AF: 0.134 AC: 1420 AN: 10576

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11600 AN: 67972

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.166 Hom.: 6667

Bravo AF: 0.173

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.67
PhyloP100		-0.40
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: rs245914; hg19: chr7-29218159;