rs2171492

Variant names:

• chr7-130310900-G-T
• rs2171492
• NM_016352.4:c.907G>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.907G>T​(p.Gly303Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,613,408 control chromosomes in the GnomAD database, including 110,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (8671 hom., cov: 32)
  • Exomes 𝑓: 0.37 (102065 hom.)
• Consequence: CPA4 NM_016352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 41 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 (MetaRNN=0.008575439).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA4	NM_016352.4	c.907G>T	p.Gly303Cys	missense_variant	Exon 9 of 11	ENST00000222482.10	NP_057436.2
CPA4	NM_001163446.2	c.808G>T	p.Gly270Cys	missense_variant	Exon 8 of 10		NP_001156918.1
CPA4	XM_047420438.1	c.595G>T	p.Gly199Cys	missense_variant	Exon 9 of 11		XP_047276394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA4	ENST00000222482.10	c.907G>T	p.Gly303Cys	missense_variant	Exon 9 of 11	1	NM_016352.4	ENSP00000222482.4
CPA4	ENST00000445470.6	c.808G>T	p.Gly270Cys	missense_variant	Exon 8 of 10	2		ENSP00000412947.2
CPA4	ENST00000493259.5	c.595G>T	p.Gly199Cys	missense_variant	Exon 7 of 9	2		ENSP00000419660.1
CPA4	ENST00000488025.1	n.380G>T		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50351 AN: 151896 Hom.: 8672 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.349 AC: 87711 AN: 251456 AF XY: 0.356

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.364

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.372 AC: 543491 AN: 1461394 Hom.: 102065 Cov.: 38 AF XY: 0.372 AC XY: 270456 AN XY: 727040

African (AFR) AF: 0.225 AC: 7544 AN: 33470

American (AMR) AF: 0.267 AC: 11931 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9209 AN: 26134

East Asian (EAS) AF: 0.349 AC: 13847 AN: 39698

South Asian (SAS) AF: 0.371 AC: 31989 AN: 86254

European-Finnish (FIN) AF: 0.358 AC: 19134 AN: 53418

Middle Eastern (MID) AF: 0.350 AC: 2016 AN: 5768

European-Non Finnish (NFE) AF: 0.383 AC: 426181 AN: 1111548

Other (OTH) AF: 0.358 AC: 21640 AN: 60382

GnomAD4 genome AF: 0.331 AC: 50366 AN: 152014 Hom.: 8671 Cov.: 32 AF XY: 0.332 AC XY: 24651 AN XY: 74302

African (AFR) AF: 0.231 AC: 9561 AN: 41470

American (AMR) AF: 0.302 AC: 4607 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1857 AN: 5144

South Asian (SAS) AF: 0.372 AC: 1790 AN: 4812

European-Finnish (FIN) AF: 0.357 AC: 3774 AN: 10574

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26430 AN: 67960

Other (OTH) AF: 0.335 AC: 705 AN: 2106

Alfa AF: 0.370 Hom.: 47534

Bravo AF: 0.322

TwinsUK AF: 0.389 AC: 1442

ALSPAC AF: 0.384 AC: 1481

ESP6500AA AF: 0.228 AC: 1003

ESP6500EA AF: 0.385 AC: 3310

ExAC AF: 0.348 AC: 42227

Asia WGS AF: 0.388 AC: 1350 AN: 3478

EpiCase AF: 0.390

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T;.;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.42	.;T;T;T
MetaRNN	Benign	0.0086	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.060	N;.;.;N
PhyloP100		-0.018
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.92	.;N;N;N
REVEL	Benign	0.035
Sift	Benign	0.082	.;T;T;T
Sift4G	Benign	0.084	.;T;T;T
Polyphen		0.0040	B;.;.;B
Vest4		0.16, 0.085, 0.13
MPC		0.12
ClinPred		0.0069	T
GERP RS		0.48
Varity_R		0.43
gMVP		0.59
Mutation Taster		=98/2	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: rs2171492; hg19: chr7-129950740; COSMIC: COSV55982488; COSMIC: COSV55982488;