5-35910427-C-T

Variant names:

• chr5-35910427-C-T
• rs1445898
• NM_001042625.2:c.254G>A

Variant summary

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

The NM_001042625.2(CAPSL):​c.254G>A​(p.Arg85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,522 control chromosomes in the GnomAD database, including 180,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.43 (14975 hom., cov: 32)
  • Exomes 𝑓: 0.47 (165502 hom.)
• Consequence: CAPSL NM_001042625.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 64 publications found

Genes affected

CAPSL (HGNC:28375): (calcyphosine like) Predicted to enable calcium ion binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.4780674E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPSL	NM_001042625.2	c.254G>A	p.Arg85Gln	missense_variant	Exon 3 of 5	ENST00000651391.1	NP_001036090.1
CAPSL	NM_144647.4	c.254G>A	p.Arg85Gln	missense_variant	Exon 3 of 5		NP_653248.3
CAPSL	XM_006714444.4	c.305G>A	p.Arg102Gln	missense_variant	Exon 3 of 5		XP_006714507.1
CAPSL	XM_006714445.4	c.305G>A	p.Arg102Gln	missense_variant	Exon 3 of 5		XP_006714508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPSL	ENST00000651391.1	c.254G>A	p.Arg85Gln	missense_variant	Exon 3 of 5		NM_001042625.2	ENSP00000498465.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64658 AN: 151864 Hom.: 14953 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.515 AC: 129341 AN: 251170 AF XY: 0.517

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.745

Gnomad FIN exome AF: 0.490

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.466 AC: 680992 AN: 1460540 Hom.: 165502 Cov.: 37 AF XY: 0.472 AC XY: 342963 AN XY: 726624

African (AFR) AF: 0.265 AC: 8864 AN: 33450

American (AMR) AF: 0.667 AC: 29806 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 11381 AN: 26118

East Asian (EAS) AF: 0.772 AC: 30637 AN: 39664

South Asian (SAS) AF: 0.656 AC: 56495 AN: 86178

European-Finnish (FIN) AF: 0.489 AC: 26122 AN: 53390

Middle Eastern (MID) AF: 0.429 AC: 2471 AN: 5764

European-Non Finnish (NFE) AF: 0.438 AC: 486506 AN: 1110938

Other (OTH) AF: 0.476 AC: 28710 AN: 60342

GnomAD4 genome AF: 0.426 AC: 64719 AN: 151982 Hom.: 14975 Cov.: 32 AF XY: 0.437 AC XY: 32468 AN XY: 74276

African (AFR) AF: 0.268 AC: 11130 AN: 41456

American (AMR) AF: 0.545 AC: 8329 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3464

East Asian (EAS) AF: 0.745 AC: 3855 AN: 5172

South Asian (SAS) AF: 0.672 AC: 3232 AN: 4812

European-Finnish (FIN) AF: 0.493 AC: 5201 AN: 10552

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30064 AN: 67932

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.442 Hom.: 59562

Bravo AF: 0.419

TwinsUK AF: 0.441 AC: 1635

ALSPAC AF: 0.446 AC: 1720

ESP6500AA AF: 0.277 AC: 1220

ESP6500EA AF: 0.444 AC: 3821

ExAC AF: 0.505 AC: 61323

Asia WGS AF: 0.688 AC: 2393 AN: 3478

EpiCase AF: 0.433

EpiControl AF: 0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.81
DEOGEN2	Benign	0.063	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.77	.;T;T;T
MetaRNN	Benign	0.0000015	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;N;.;.
PhyloP100		-0.98
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.83	N;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.068
MPC		0.019
ClinPred		0.00077	T
GERP RS		0.53
Varity_R		0.035
gMVP		0.43
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: rs1445898; hg19: chr5-35910529; COSMIC: COSV107509223;