7-128759170-A-G

Variant names:

• chr7-128759170-A-G
• rs339097
• NM_001219.5:c.582+133A>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.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
• Publications: 32 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=-0.94).
• 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 rank	MANE	Protein	UniProt
CALU	NM_001219.5	c.582+133A>G		intron_variant	Intron 4 of 6	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.582+133A>G		intron_variant	Intron 4 of 6	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

African (AFR) AF: 0.127 AC: 1414 AN: 11142

American (AMR) AF: 0.0105 AC: 133 AN: 12710

Ashkenazi Jewish (ASJ) AF: 0.00106 AC: 13 AN: 12284

East Asian (EAS) AF: 0.0239 AC: 644 AN: 26934

South Asian (SAS) AF: 0.00181 AC: 41 AN: 22698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35060

Middle Eastern (MID) AF: 0.00849 AC: 16 AN: 1884

European-Non Finnish (NFE) AF: 0.000533 AC: 171 AN: 320822

Other (OTH) AF: 0.0126 AC: 318 AN: 25242

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

African (AFR) AF: 0.130 AC: 5413 AN: 41490

American (AMR) AF: 0.0163 AC: 249 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5192

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68036

Other (OTH) AF: 0.0384 AC: 81 AN: 2108

Alfa AF: 0.0176 Hom.: 276

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
PhyloP100		0.35
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs339097; hg19: chr7-128399224;