NM_016352.4:c.703-134G>C

Variant names:

• chr7-130308173-G-C
• rs1038628
• NM_016352.4:c.703-134G>C

Variant summary

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

The NM_016352.4(CPA4):​c.703-134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 573,846 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 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: 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA4	NM_016352.4	c.703-134G>C		intron_variant	Intron 7 of 10	ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.604-134G>C		intron_variant	Intron 6 of 9		NP_001156918.1
CPA4	XM_047420438.1	c.391-134G>C		intron_variant	Intron 7 of 10		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.703-134G>C		intron_variant	Intron 7 of 10	1	NM_016352.4	ENSP00000222482.4
CPA4	ENST00000488025.1	n.42G>C		non_coding_transcript_exon_variant	Exon 1 of 3	4
CPA4	ENST00000445470.6	c.604-134G>C		intron_variant	Intron 6 of 9	2		ENSP00000412947.2
CPA4	ENST00000493259.5	c.391-134G>C		intron_variant	Intron 5 of 8	2		ENSP00000419660.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000174 AC: 1 AN: 573846 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 307880

African (AFR) AF: 0.00 AC: 0 AN: 16074

American (AMR) AF: 0.00 AC: 0 AN: 33592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17346

East Asian (EAS) AF: 0.00 AC: 0 AN: 34760

South Asian (SAS) AF: 0.00 AC: 0 AN: 58108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.00000301 AC: 1 AN: 332184

Other (OTH) AF: 0.00 AC: 0 AN: 30700

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1038628; hg19: chr7-129948013;