7-71810392-T-G

Variant names:

• chr7-71810392-T-G
• rs911140713
• NM_031468.4:c.602A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_031468.4(CALN1):​c.602A>C​(p.Asn201Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. N201S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CALN1 NM_031468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19501877).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.602A>C	p.Asn201Thr	missense	Exon 6 of 7	NP_113656.2	Q9BXU9-2
	CALN1	NM_001017440.3		c.476A>C	p.Asn159Thr	missense	Exon 5 of 6	NP_001017440.1	Q9BXU9-1
	CALN1	NM_001363460.1		c.476A>C	p.Asn159Thr	missense	Exon 5 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.602A>C	p.Asn201Thr	missense	Exon 6 of 7	ENSP00000378690.2	Q9BXU9-2
	CALN1	ENST00000329008.9	TSL:1	c.476A>C	p.Asn159Thr	missense	Exon 5 of 6	ENSP00000332498.5	Q9BXU9-1
	CALN1	ENST00000395276.6	TSL:1	c.476A>C	p.Asn159Thr	missense	Exon 6 of 7	ENSP00000378691.2	Q9BXU9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N
PhyloP100		6.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.36
MutPred		0.42		Gain of glycosylation at N159 (P = 0.0665)
MVP		0.49
MPC		0.78
ClinPred		0.80	D
GERP RS		5.1
PromoterAI		0.0030	Neutral
Varity_R		0.18
gMVP		0.76
Mutation Taster		=38/62	disease causing

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: rs911140713; hg19: chr7-71275377;