11-32091433-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002901.4(RCN1):c.237G>C(p.Glu79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,547,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RCN1
NM_002901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Publications

0 publications found

Variant links:

Genes affected

RCN1 (HGNC:9934): (reticulocalbin 1) Reticulocalbin 1 is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. High conservation of amino acid residues outside of these motifs, in comparison to mouse reticulocalbin, is consistent with a possible biochemical function besides that of calcium binding. In human endothelial and prostate cancer cell lines this protein localizes to the plasma membrane.[provided by RefSeq, Jan 2009]

RCN1 links:

ENSG00000285283 (HGNC:):

ENSG00000285283 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.3852792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCN1	NM_002901.4 link	c.237G>C	p.Glu79Asp	missense_variant	Exon 1 of 6	ENST00000054950.4	NP_002892.1	Q15293-1V9HW95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCN1	ENST00000054950.4 link	c.237G>C	p.Glu79Asp	missense_variant	Exon 1 of 6	1	NM_002901.4	ENSP00000054950.4	Q15293-1
ENSG00000285283	ENST00000532942.5 link	c.102-5711G>C		intron_variant	Intron 1 of 5	2		ENSP00000436422.1
ENSG00000285283	ENST00000530348.5 link	c.-244-5711G>C		intron_variant	Intron 1 of 3	4		ENSP00000436482.1	E9PP27
RCN1	ENST00000532721.1 link	c.-612G>C		upstream_gene_variant		3		ENSP00000433249.1	E9PLM2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000657

AC:

AN:

152250

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1395056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31120

American (AMR)

AF:

0.0000565

AC:

AN:

35410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25060

East Asian (EAS)

AF:

0.00

AC:

AN:

35462

South Asian (SAS)

AF:

0.00

AC:

AN:

78538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077458

Other (OTH)

AF:

0.00

AC:

AN:

57868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.237G>C (p.E79D) alteration is located in exon 1 (coding exon 1) of the RCN1 gene. This alteration results from a G to C substitution at nucleotide position 237, causing the glutamic acid (E) at amino acid position 79 to be replaced by an aspartic acid (D). 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

0.82

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.087

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

3.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.25

Vest4

0.60

MutPred

0.54

Loss of loop (P = 0.1258);

MVP

0.33

MPC

1.1

ClinPred

0.78

GERP RS

3.1

PromoterAI

0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.61

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-32091433-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over