NM_001219.5:c.*4A>G

Variant names:

• chr7-128769171-A-G
• rs1043550
• NM_001219.5:c.*4A>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.*4A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,472,348 control chromosomes in the GnomAD database, including 104,308 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 0.30 (8087 hom., cov: 31)
  • Exomes 𝑓: 0.37 (96221 hom.)
• Consequence: CALU NM_001219.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 35 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 = 0.406 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.*4A>G		3_prime_UTR	Exon 7 of 7	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.*4A>G		3_prime_UTR	Exon 8 of 8	NP_001186600.1	O43852-3
	CALU	NM_001199672.2		c.*4A>G		3_prime_UTR	Exon 8 of 8	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.*4A>G		3_prime_UTR	Exon 7 of 7	ENSP00000249364.4	O43852-1
	CALU	ENST00000479257.5	TSL:1	c.*4A>G		3_prime_UTR	Exon 8 of 8	ENSP00000420381.1	O43852-3
	CALU	ENST00000542996.7	TSL:1	c.*4A>G		3_prime_UTR	Exon 8 of 8	ENSP00000438248.1	O43852-4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45617 AN: 151932 Hom.: 8083 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.311 AC: 72201 AN: 232266 AF XY: 0.319

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.0578

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.370 AC: 488908 AN: 1320298 Hom.: 96221 Cov.: 19 AF XY: 0.368 AC XY: 243756 AN XY: 662748

African (AFR) AF: 0.141 AC: 4244 AN: 30196

American (AMR) AF: 0.244 AC: 9460 AN: 38798

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 9536 AN: 24470

East Asian (EAS) AF: 0.0607 AC: 2365 AN: 38962

South Asian (SAS) AF: 0.211 AC: 16809 AN: 79478

European-Finnish (FIN) AF: 0.328 AC: 17380 AN: 53026

Middle Eastern (MID) AF: 0.393 AC: 2151 AN: 5476

European-Non Finnish (NFE) AF: 0.410 AC: 407674 AN: 994194

Other (OTH) AF: 0.346 AC: 19289 AN: 55698

GnomAD4 genome AF: 0.300 AC: 45619 AN: 152050 Hom.: 8087 Cov.: 31 AF XY: 0.294 AC XY: 21870 AN XY: 74324

African (AFR) AF: 0.148 AC: 6137 AN: 41460

American (AMR) AF: 0.268 AC: 4089 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.0685 AC: 355 AN: 5182

South Asian (SAS) AF: 0.199 AC: 960 AN: 4822

European-Finnish (FIN) AF: 0.335 AC: 3536 AN: 10562

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27890 AN: 67952

Other (OTH) AF: 0.326 AC: 688 AN: 2112

Alfa AF: 0.374 Hom.: 48347

Bravo AF: 0.293

Asia WGS AF: 0.128 AC: 444 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.49
PhyloP100		0.039
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)		0.010		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: rs1043550; hg19: chr7-128409225; COSMIC: COSV50821391; COSMIC: COSV50821391;