1-207454348-T-C

Variant names:

• chr1-207454348-T-C
• rs3813946
• NM_001006658.3:c.-71T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001006658.3(CR2):​c.-71T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,339,174 control chromosomes in the GnomAD database, including 25,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.20 (23960 hom.)
• Consequence: CR2 NM_001006658.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.882
• Publications: 32 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency, common variable, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-207454348-T-C is Benign according to our data. Variant chr1-207454348-T-C is described in ClinVar as [Benign]. Clinvar id is 478828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.-71T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 20	ENST00000367057.8	NP_001006659.1
CR2	NM_001006658.3	c.-71T>C		5_prime_UTR_variant	Exon 1 of 20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.-71T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19		NP_001868.2
CR2	NM_001877.5	c.-71T>C		5_prime_UTR_variant	Exon 1 of 19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.-71T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 20	1	NM_001006658.3	ENSP00000356024.3
CR2	ENST00000367057.8	c.-71T>C		5_prime_UTR_variant	Exon 1 of 20	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24052 AN: 152074 Hom.: 2032 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.196 AC: 232140 AN: 1186982 Hom.: 23960 Cov.: 17 AF XY: 0.196 AC XY: 116461 AN XY: 595314

African (AFR) AF: 0.0856 AC: 2401 AN: 28048

American (AMR) AF: 0.121 AC: 4297 AN: 35626

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5194 AN: 23800

East Asian (EAS) AF: 0.121 AC: 4266 AN: 35162

South Asian (SAS) AF: 0.167 AC: 12629 AN: 75468

European-Finnish (FIN) AF: 0.160 AC: 5632 AN: 35130

Middle Eastern (MID) AF: 0.252 AC: 1187 AN: 4704

European-Non Finnish (NFE) AF: 0.208 AC: 186780 AN: 897698

Other (OTH) AF: 0.190 AC: 9754 AN: 51346

GnomAD4 genome AF: 0.158 AC: 24057 AN: 152192 Hom.: 2032 Cov.: 32 AF XY: 0.155 AC XY: 11552 AN XY: 74430

African (AFR) AF: 0.0887 AC: 3685 AN: 41526

American (AMR) AF: 0.142 AC: 2170 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3466

East Asian (EAS) AF: 0.106 AC: 548 AN: 5166

South Asian (SAS) AF: 0.167 AC: 807 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1771 AN: 10606

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13722 AN: 67988

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.0909 Hom.: 128

Bravo AF: 0.154

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 7 Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22673213, 23612877, 17360460) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		-0.88
PromoterAI		0.058	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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: rs3813946; hg19: chr1-207627693;