rs2307040

Positions:

• chr7-128754552-C-G
• chr7-128754552-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000542996.7(CALU):​c.269C>G​(p.Ala90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict 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: 32)
• Consequence: CALU ENST00000542996.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13192031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALU	NM_001219.5	c.415+97C>G		intron_variant		ENST00000249364.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALU	ENST00000249364.9	c.415+97C>G		intron_variant		1	NM_001219.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.60
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.17
Sift	Benign	0.50	T;T
Sift4G	Benign	0.40	T;T
Vest4		0.11
MutPred		0.76		Loss of stability (P = 0.0258);.;
MVP		0.81
MPC		0.33
ClinPred		0.023	T
GERP RS		0.24
gMVP		0.23

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: rs2307040; hg19: chr7-128394606;