7-72023704-C-G

Variant names:

• chr7-72023704-C-G
• rs557342382
• NM_031468.4:c.454G>C

Variant summary

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

The NM_031468.4(CALN1):​c.454G>C​(p.Gly152Arg) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G152S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALN1 NM_031468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 0 publications found

Genes affected

CALN1 (HGNC:13248): (calneuron 1) This gene encodes a protein with high similarity to the calcium-binding proteins of the calmodulin family. The encoded protein contains two EF-hand domains and potential calcium-binding sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 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=0.273335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031468.4. 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
	CALN1	NM_031468.4	MANE Select	c.454G>C	p.Gly152Arg	missense	Exon 5 of 7	NP_113656.2	Q9BXU9-2
	CALN1	NM_001017440.3		c.328G>C	p.Gly110Arg	missense	Exon 4 of 6	NP_001017440.1	Q9BXU9-1
	CALN1	NM_001363460.1		c.328G>C	p.Gly110Arg	missense	Exon 4 of 6	NP_001350389.1	A4D1Z1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALN1	ENST00000395275.7	TSL:5 MANE Select	c.454G>C	p.Gly152Arg	missense	Exon 5 of 7	ENSP00000378690.2	Q9BXU9-2
	CALN1	ENST00000329008.9	TSL:1	c.328G>C	p.Gly110Arg	missense	Exon 4 of 6	ENSP00000332498.5	Q9BXU9-1
	CALN1	ENST00000395276.6	TSL:1	c.328G>C	p.Gly110Arg	missense	Exon 5 of 7	ENSP00000378691.2	Q9BXU9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.090
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.069
Sift	Benign	0.13	T
Sift4G	Benign	0.53	T
Polyphen		0.070	B
Vest4		0.36
MutPred		0.35		Gain of solvent accessibility (P = 0.0097)
MVP		0.64
MPC		1.7
ClinPred		0.73	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.70
Mutation Taster		=52/48	polymorphism

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: rs557342382; hg19: chr7-71488689;