7-130308173-G-T

Variant names:

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

Variant summary

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

The NM_016352.4(CPA4):​c.703-134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 724,972 control chromosomes in the GnomAD database, including 49,622 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 0.33 (8861 hom., cov: 32)
  • Exomes 𝑓: 0.37 (40761 hom.)
• Consequence: CPA4 NM_016352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	NM_016352.4	MANE Select	c.703-134G>T		intron	N/A	NP_057436.2	A4D1M3
	CPA4	NM_001163446.2		c.604-134G>T		intron	N/A	NP_001156918.1	Q9UI42-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA4	ENST00000222482.10	TSL:1 MANE Select	c.703-134G>T		intron	N/A	ENSP00000222482.4	Q9UI42-1
	CPA4	ENST00000445470.6	TSL:2	c.604-134G>T		intron	N/A	ENSP00000412947.2	Q9UI42-2
	CPA4	ENST00000493259.5	TSL:2	c.391-134G>T		intron	N/A	ENSP00000419660.1	B7Z5J4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50566 AN: 151924 Hom.: 8861 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.373 AC: 213783 AN: 572930 Hom.: 40761 Cov.: 6 AF XY: 0.374 AC XY: 115092 AN XY: 307368

African (AFR) AF: 0.206 AC: 3308 AN: 16060

American (AMR) AF: 0.271 AC: 9065 AN: 33500

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 6471 AN: 17318

East Asian (EAS) AF: 0.334 AC: 11581 AN: 34710

South Asian (SAS) AF: 0.378 AC: 21907 AN: 58030

European-Finnish (FIN) AF: 0.362 AC: 17053 AN: 47110

Middle Eastern (MID) AF: 0.374 AC: 1456 AN: 3890

European-Non Finnish (NFE) AF: 0.397 AC: 131750 AN: 331642

Other (OTH) AF: 0.365 AC: 11192 AN: 30670

GnomAD4 genome AF: 0.333 AC: 50584 AN: 152042 Hom.: 8861 Cov.: 32 AF XY: 0.334 AC XY: 24810 AN XY: 74278

African (AFR) AF: 0.208 AC: 8625 AN: 41502

American (AMR) AF: 0.316 AC: 4832 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1759 AN: 5156

South Asian (SAS) AF: 0.382 AC: 1838 AN: 4810

European-Finnish (FIN) AF: 0.359 AC: 3790 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27273 AN: 67950

Other (OTH) AF: 0.341 AC: 716 AN: 2102

Alfa AF: 0.351 Hom.: 1284

Bravo AF: 0.323

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		-1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1038628;

hg19: chr7-129948013;

COSMIC: COSV55983792;

COSMIC: COSV55983792;