rs112859639

Variant names:

• chr1-207485454-TTC-T
• rs112859639
• NM_001006658.3:c.3189-8_3189-7delCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001006658.3(CR2):​c.3189-8_3189-7delCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000753 in 1,544,162 control chromosomes in the GnomAD database, including 13 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (7 hom.)
• Consequence: CR2 NM_001006658.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0420

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-207485454-TTC-T is Benign according to our data. Variant chr1-207485454-TTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 473099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00375 (571/152358) while in subpopulation AFR AF= 0.0128 (533/41588). AF 95% confidence interval is 0.0119. There are 6 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.3189-8_3189-7delCT		splice_region_variant, intron_variant	Intron 18 of 19	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.3012-8_3012-7delCT		splice_region_variant, intron_variant	Intron 17 of 18		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.3189-9_3189-8delTC		splice_region_variant, intron_variant	Intron 18 of 19	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152240 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00101 AC: 254 AN: 250492 Hom.: 2 AF XY: 0.000664 AC XY: 90 AN XY: 135594

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000425 AC: 591 AN: 1391804 Hom.: 7 AF XY: 0.000360 AC XY: 251 AN XY: 696572

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000267

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00375 AC: 571 AN: 152358 Hom.: 6 Cov.: 31 AF XY: 0.00383 AC XY: 285 AN XY: 74502

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00185 Hom.: 1

Bravo AF: 0.00423

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency, common variable, 7 Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CR2-related disorder Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Jun 05, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs112859639; hg19: chr1-207658799;