Variant chr7-71787867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_031468.4(CALN1):c.694C>T(p.Arg232Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CALN1
NM_031468.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

Variant links:

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]

CALN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.744

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALN1	NM_031468.4 linkuse as main transcript	c.694C>T	p.Arg232Trp	missense_variant	7/7	ENST00000395275.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALN1	ENST00000395275.7 linkuse as main transcript	c.694C>T	p.Arg232Trp	missense_variant	7/7	5	NM_031468.4		Q9BXU9-2
CALN1	ENST00000329008.9 linkuse as main transcript	c.568C>T	p.Arg190Trp	missense_variant	6/6	1		P1	Q9BXU9-1
CALN1	ENST00000395276.6 linkuse as main transcript	c.568C>T	p.Arg190Trp	missense_variant	7/7	1		P1	Q9BXU9-1
CALN1	ENST00000431984.5 linkuse as main transcript	c.568C>T	p.Arg190Trp	missense_variant	6/6	1		P1	Q9BXU9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251406

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.694C>T (p.R232W) alteration is located in exon 7 (coding exon 6) of the CALN1 gene. This alteration results from a C to T substitution at nucleotide position 694, causing the arginine (R) at amino acid position 232 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;.;T;.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.61

LIST_S2

Pathogenic

0.98

.;D;.;D;D

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.74

D;D;D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.1

L;.;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.5

D;D;D;D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;.;D;.;D

Vest4

0.84

MutPred

0.37

Gain of ubiquitination at K191 (P = 0.0331);.;Gain of ubiquitination at K191 (P = 0.0331);.;Gain of ubiquitination at K191 (P = 0.0331);

MVP

0.72

MPC

1.9

ClinPred

0.99

GERP RS

3.3

Varity_R

0.56

gMVP

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over