rs339097

Positions:

• chr7-128759170-A-G

Variant summary

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

The NM_001219.5(CALU):​c.582+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 621,024 control chromosomes in the GnomAD database, including 499 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 0.039 (369 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (130 hom.)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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]

CALU (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALU	NM_001219.5	c.582+133A>G		intron_variant		ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.582+133A>G		intron_variant		1	NM_001219.5	ENSP00000249364.4

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5843 AN: 152130 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0161

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0384

GnomAD4 exome AF: 0.00587 AC: 2750 AN: 468776 Hom.: 130 AF XY: 0.00518 AC XY: 1240 AN XY: 239608

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.0239

Gnomad4 SAS exome AF: 0.00181

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000533

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0387 AC: 5896 AN: 152248 Hom.: 369 Cov.: 32 AF XY: 0.0364 AC XY: 2713 AN XY: 74440

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0203 Hom.: 32

Bravo AF: 0.0445

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.51
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: rs339097; hg19: chr7-128399224;