7-128748594-G-C

Variant names:

• chr7-128748594-G-C
• rs2290228
• NM_001219.5:c.11G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001219.5(CALU):​c.11G>C​(p.Arg4Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CALU NM_001219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32908177).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	NM_001219.5	MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 2 of 7	NP_001210.1
	CALU	NM_001199671.2		c.35G>C	p.Arg12Pro	missense	Exon 3 of 8	NP_001186600.1
	CALU	NM_001199672.2		c.35G>C	p.Arg12Pro	missense	Exon 3 of 8	NP_001186601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.11G>C	p.Arg4Pro	missense	Exon 2 of 7	ENSP00000249364.4
	CALU	ENST00000479257.5	TSL:1	c.35G>C	p.Arg12Pro	missense	Exon 3 of 8	ENSP00000420381.1
	CALU	ENST00000542996.7	TSL:1	c.35G>C	p.Arg12Pro	missense	Exon 3 of 8	ENSP00000438248.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.22
Sift	Benign	0.063	T
Sift4G	Benign	0.35	T
Polyphen		0.0050	B
Vest4		0.13
MutPred		0.35		Gain of disorder (P = 0.0769)
MVP		0.38
MPC		0.49
ClinPred		0.66	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.55
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2290228; hg19: chr7-128388648;