rs12538139

Variant names:

• chr7-128748487-G-A
• rs12538139
• NM_001219.5:c.-11-86G>A

Variant summary

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

The NM_001219.5(CALU):​c.-11-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,206,580 control chromosomes in the GnomAD database, including 73,924 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 (6857 hom., cov: 33)
  • Exomes 𝑓: 0.34 (67067 hom.)
• Consequence: CALU NM_001219.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALU	NM_001219.5	c.-11-86G>A		intron_variant	Intron 1 of 6	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALU	ENST00000249364.9	c.-11-86G>A		intron_variant	Intron 1 of 6	1	NM_001219.5	ENSP00000249364.4

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42123 AN: 152048 Hom.: 6853 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.345 AC: 363758 AN: 1054412 Hom.: 67067 Cov.: 13 AF XY: 0.342 AC XY: 181802 AN XY: 531442

African (AFR) AF: 0.134 AC: 3201 AN: 23812

American (AMR) AF: 0.227 AC: 5743 AN: 25280

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 7743 AN: 20706

East Asian (EAS) AF: 0.0616 AC: 2166 AN: 35188

South Asian (SAS) AF: 0.207 AC: 13612 AN: 65704

European-Finnish (FIN) AF: 0.281 AC: 12502 AN: 44510

Middle Eastern (MID) AF: 0.388 AC: 1847 AN: 4766

European-Non Finnish (NFE) AF: 0.383 AC: 302164 AN: 788462

Other (OTH) AF: 0.321 AC: 14780 AN: 45984

GnomAD4 genome AF: 0.277 AC: 42128 AN: 152168 Hom.: 6857 Cov.: 33 AF XY: 0.271 AC XY: 20141 AN XY: 74392

African (AFR) AF: 0.141 AC: 5864 AN: 41526

American (AMR) AF: 0.251 AC: 3835 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3466

East Asian (EAS) AF: 0.0693 AC: 359 AN: 5182

South Asian (SAS) AF: 0.194 AC: 935 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10584

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

European-Non Finnish (NFE) AF: 0.376 AC: 25560 AN: 67982

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.307 Hom.: 1008

Bravo AF: 0.273

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.38
PhyloP100		-0.51
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: rs12538139; hg19: chr7-128388541;