rs2290227

Positions:

• chr7-128748927-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001219.5(CALU):​c.221+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 631,330 control chromosomes in the GnomAD database, including 1,039 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 0.047 (235 hom., cov: 33)
  • Exomes 𝑓: 0.052 (804 hom.)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALU	NM_001219.5	c.221+123G>A		intron_variant		ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.221+123G>A		intron_variant		1	NM_001219.5	ENSP00000249364

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7106 AN: 152100 Hom.: 233 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0430

GnomAD4 exome AF: 0.0524 AC: 25088 AN: 479112 Hom.: 804 AF XY: 0.0540 AC XY: 13518 AN XY: 250442

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.0683

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.0977

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.0624

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0490

GnomAD4 genome AF: 0.0467 AC: 7112 AN: 152218 Hom.: 235 Cov.: 33 AF XY: 0.0490 AC XY: 3648 AN XY: 74428

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0446 Hom.: 55

Bravo AF: 0.0448

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2290227; hg19: chr7-128388981;