Variant chr1-207472818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000367057.8(CR2):c.1617C>T(p.Thr539=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,944 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 45 hom., cov: 32)

Exomes 𝑓: 0.014 ( 208 hom. )

Consequence

CR2
ENST00000367057.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

CR2 (HGNC:2336): (complement C3d receptor 2) This gene encodes a membrane protein, which functions as a receptor for Epstein-Barr virus (EBV) binding on B and T lymphocytes. Genetic variations in this gene are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

CR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019263625).

BP6

Variant 1-207472818-C-T is Benign according to our data. Variant chr1-207472818-C-T is described in ClinVar as [Benign]. Clinvar id is 473095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207472818-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0209 (3189/152252) while in subpopulation AFR AF= 0.032 (1329/41534). AF 95% confidence interval is 0.0306. There are 45 homozygotes in gnomad4. There are 1512 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR2	NM_001006658.3 linkuse as main transcript	c.1617C>T	p.Thr539=	synonymous_variant	10/20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5 linkuse as main transcript	c.1617C>T	p.Thr539=	synonymous_variant	10/19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 linkuse as main transcript	c.1617C>T	p.Thr539=	synonymous_variant	10/20	1	NM_001006658.3	ENSP00000356024	P1	P20023-3

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3190

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0151

AC:

3806

AN:

251298

Hom.:

AF XY:

0.0150

AC XY:

2032

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0143

AC:

20902

AN:

1461692

Hom.:

208

Cov.:

AF XY:

0.0142

AC XY:

10350

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00552

Gnomad4 FIN exome

AF:

0.0154

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0209

AC:

3189

AN:

152252

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1512

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0320

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0359

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0219

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.0166

AC:

143

ExAC

AF:

0.0153

AC:

1854

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0168

EpiControl

AF:

0.0187

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.58

DANN

Benign

0.85

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;N

GERP RS

-5.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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