7-128754552-C-T

Variant names:

• chr7-128754552-C-T
• rs2307040
• ENST00000542996.7:c.269C>T

Variant summary

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

The NM_001199672.2(CALU):​c.269C>T​(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,555,712 control chromosomes in the GnomAD database, including 96,989 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.28 (6867 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90122 hom.)
• Consequence: CALU NM_001199672.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 28 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=5.4627657E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199672.2. 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
	CALU	NM_001219.5	MANE Select	c.415+97C>T		intron	N/A	NP_001210.1	Q6IAW5
	CALU	NM_001199672.2		c.269C>T	p.Ala90Val	missense	Exon 4 of 8	NP_001186601.1	O43852-4
	CALU	NM_001130674.3		c.245C>T	p.Ala82Val	missense	Exon 3 of 7	NP_001124146.1	O43852-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000542996.7	TSL:1	c.269C>T	p.Ala90Val	missense	Exon 4 of 8	ENSP00000438248.1	O43852-4
	CALU	ENST00000449187.7	TSL:1	c.245C>T	p.Ala82Val	missense	Exon 3 of 7	ENSP00000408838.2	O43852-2
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.415+97C>T		intron	N/A	ENSP00000249364.4	O43852-1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42132 AN: 151910 Hom.: 6863 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.284 AC: 47226 AN: 166120 AF XY: 0.289

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.0509

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.348 AC: 489163 AN: 1403684 Hom.: 90122 Cov.: 32 AF XY: 0.346 AC XY: 239616 AN XY: 693040

African (AFR) AF: 0.138 AC: 4402 AN: 31908

American (AMR) AF: 0.228 AC: 8200 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9457 AN: 25188

East Asian (EAS) AF: 0.0547 AC: 1991 AN: 36372

South Asian (SAS) AF: 0.209 AC: 16671 AN: 79848

European-Finnish (FIN) AF: 0.281 AC: 14093 AN: 50080

Middle Eastern (MID) AF: 0.386 AC: 2201 AN: 5700

European-Non Finnish (NFE) AF: 0.383 AC: 413371 AN: 1080298

Other (OTH) AF: 0.322 AC: 18777 AN: 58284

GnomAD4 genome AF: 0.277 AC: 42134 AN: 152028 Hom.: 6867 Cov.: 32 AF XY: 0.271 AC XY: 20137 AN XY: 74324

African (AFR) AF: 0.144 AC: 5955 AN: 41456

American (AMR) AF: 0.250 AC: 3819 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3472

East Asian (EAS) AF: 0.0572 AC: 296 AN: 5176

South Asian (SAS) AF: 0.194 AC: 935 AN: 4812

European-Finnish (FIN) AF: 0.287 AC: 3031 AN: 10546

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25562 AN: 67980

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.326 Hom.: 6150

Bravo AF: 0.273

TwinsUK AF: 0.378 AC: 1403

ALSPAC AF: 0.378 AC: 1455

ESP6500AA AF: 0.131 AC: 181

ESP6500EA AF: 0.371 AC: 1182

ExAC AF: 0.229 AC: 24022

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.97
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.00055	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.32
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.26	T
Sift4G	Benign	0.30	T
Vest4		0.027
MPC		0.33
ClinPred		0.0011	T
GERP RS		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.26
Mutation Taster		=99/1	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: rs2307040; hg19: chr7-128394606; COSMIC: COSV50821389; COSMIC: COSV50821389;