chr7-130294379-T-C

Variant names:

• chr7-130294379-T-C
• rs3807344
• NM_016352.4:c.68+1131T>C

Variant summary

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

The NM_016352.4(CPA4):​c.68+1131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,066 control chromosomes in the GnomAD database, including 10,200 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 0.36 (10200 hom., cov: 32)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 11 publications found

Genes affected

CPA4 (HGNC:15740): (carboxypeptidase A4) This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016352.4. 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
	CPA4	NM_016352.4	MANE Select	c.68+1131T>C		intron	N/A	NP_057436.2
	CPA4	NM_001163446.2		c.68+1131T>C		intron	N/A	NP_001156918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	ENST00000222482.10	TSL:1 MANE Select	c.68+1131T>C		intron	N/A	ENSP00000222482.4
	CPA4	ENST00000474254.5	TSL:1	n.88+1131T>C		intron	N/A
	CPA4	ENST00000445470.6	TSL:2	c.68+1131T>C		intron	N/A	ENSP00000412947.2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54983 AN: 151948 Hom.: 10180 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.362 AC: 55047 AN: 152066 Hom.: 10200 Cov.: 32 AF XY: 0.367 AC XY: 27303 AN XY: 74334

African (AFR) AF: 0.331 AC: 13755 AN: 41520

American (AMR) AF: 0.447 AC: 6840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3468

East Asian (EAS) AF: 0.505 AC: 2598 AN: 5148

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4826

European-Finnish (FIN) AF: 0.408 AC: 4300 AN: 10542

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23399 AN: 67960

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.354 Hom.: 36101

Bravo AF: 0.366

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3807344; hg19: chr7-129934219; COSMIC: COSV55978818; COSMIC: COSV55978818;