rs1006023

Variant names:

• chr7-128749500-T-G
• rs1006023
• NM_001219.5:c.221+696T>G

Variant summary

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

The NM_001219.5(CALU):​c.221+696T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,944 control chromosomes in the GnomAD database, including 6,761 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.

• Frequency: Genomes: 𝑓 0.28 (6761 hom., cov: 32)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 10 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	NM_001219.5	MANE Select	c.221+696T>G		intron	N/A	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.245+696T>G		intron	N/A	NP_001186600.1	O43852-3
	CALU	NM_001199672.2		c.245+696T>G		intron	N/A	NP_001186601.1	O43852-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.221+696T>G		intron	N/A	ENSP00000249364.4	O43852-1
	CALU	ENST00000479257.5	TSL:1	c.245+696T>G		intron	N/A	ENSP00000420381.1	O43852-3
	CALU	ENST00000542996.7	TSL:1	c.245+696T>G		intron	N/A	ENSP00000438248.1	O43852-4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41932 AN: 151826 Hom.: 6757 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.276 AC: 41936 AN: 151944 Hom.: 6761 Cov.: 32 AF XY: 0.270 AC XY: 20049 AN XY: 74292

African (AFR) AF: 0.141 AC: 5831 AN: 41496

American (AMR) AF: 0.249 AC: 3798 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3462

East Asian (EAS) AF: 0.0690 AC: 358 AN: 5188

South Asian (SAS) AF: 0.193 AC: 929 AN: 4810

European-Finnish (FIN) AF: 0.287 AC: 3032 AN: 10554

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25455 AN: 67852

Other (OTH) AF: 0.303 AC: 639 AN: 2106

Alfa AF: 0.344 Hom.: 28709

Bravo AF: 0.273

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		0.38
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: rs1006023; hg19: chr7-128389554;