chr7-128748594-G-A

Variant names:

• chr7-128748594-G-A
• rs2290228
• NM_001219.5:c.11G>A

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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 0.15 (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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	NM_001219.5	MANE Select	c.11G>A	p.Arg4Gln	missense	Exon 2 of 7	NP_001210.1
	CALU	NM_001199671.2		c.35G>A	p.Arg12Gln	missense	Exon 3 of 8	NP_001186600.1
	CALU	NM_001199672.2		c.35G>A	p.Arg12Gln	missense	Exon 3 of 8	NP_001186601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.11G>A	p.Arg4Gln	missense	Exon 2 of 7	ENSP00000249364.4
	CALU	ENST00000479257.5	TSL:1	c.35G>A	p.Arg12Gln	missense	Exon 3 of 8	ENSP00000420381.1
	CALU	ENST00000542996.7	TSL:1	c.35G>A	p.Arg12Gln	missense	Exon 3 of 8	ENSP00000438248.1

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

GnomAD2 exomes AF: 0.167 AC: 41916 AN: 251026 AF XY: 0.170

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 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

African (AFR) AF: 0.105 AC: 3525 AN: 33454

American (AMR) AF: 0.157 AC: 7005 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6046 AN: 26124

East Asian (EAS) AF: 0.211 AC: 8386 AN: 39684

South Asian (SAS) AF: 0.224 AC: 19305 AN: 86180

European-Finnish (FIN) AF: 0.140 AC: 7456 AN: 53406

Middle Eastern (MID) AF: 0.181 AC: 1045 AN: 5760

European-Non Finnish (NFE) AF: 0.153 AC: 170087 AN: 1110764

Other (OTH) AF: 0.176 AC: 10594 AN: 60344

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

African (AFR) AF: 0.111 AC: 4593 AN: 41498

American (AMR) AF: 0.150 AC: 2290 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3468

East Asian (EAS) AF: 0.209 AC: 1083 AN: 5170

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1382 AN: 10580

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10550 AN: 68004

Other (OTH) AF: 0.151 AC: 319 AN: 2116

Alfa AF: 0.156 Hom.: 7906

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 v4.9

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
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.15
Sift	Benign	0.39	T
Sift4G	Benign	0.76	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
Mutation Taster		=77/23	polymorphism (auto)

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

Other links and lift over

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