rs2290228

Positions:

• chr7-128748594-G-A
• chr7-128748594-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001219.5(CALU):​c.11G>A​(p.Arg4Gln) variant causes a missense change. The variant allele was found at a frequency of 0.159 in 1,612,570 control chromosomes in the GnomAD database, including 21,307 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1786 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19521 hom.)
• Consequence: CALU NM_001219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20

Genes affected

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001409024).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALU	NM_001219.5	c.11G>A	p.Arg4Gln	missense_variant	2/7	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.11G>A	p.Arg4Gln	missense_variant	2/7	1	NM_001219.5	ENSP00000249364

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22358 AN: 152046 Hom.: 1787 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.167 AC: 41916 AN: 251026 Hom.: 3824 AF XY: 0.170 AC XY: 23114 AN XY: 135656

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.160 AC: 233449 AN: 1460406 Hom.: 19521 Cov.: 32 AF XY: 0.162 AC XY: 117728 AN XY: 726564

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.147 AC: 22365 AN: 152164 Hom.: 1786 Cov.: 33 AF XY: 0.147 AC XY: 10907 AN XY: 74378

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.151

Alfa AF: 0.159 Hom.: 4291

Bravo AF: 0.147

TwinsUK AF: 0.156 AC: 578

ALSPAC AF: 0.155 AC: 597

ESP6500AA AF: 0.110 AC: 485

ESP6500EA AF: 0.165 AC: 1415

ExAC AF: 0.168 AC: 20430

Asia WGS AF: 0.217 AC: 756 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;T;.;.
Eigen	Benign	0.067
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;T;T;T;T
MetaRNN	Benign	0.0014	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;L;.
MutationTaster	Benign	0.000082	P;P;P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.050	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.39	T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T
Polyphen		0.0030	.;.;B;.;.
Vest4		0.086
MPC		0.38
ClinPred		0.016	T
GERP RS		5.9
Varity_R		0.15
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2290228; hg19: chr7-128388648; COSMIC: COSV50821381;