ENST00000735999.1:n.263T>C

Variant names:

• chr1-207641844-A-G
• rs10494885
• ENST00000735999.1:n.263T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000735999.1(ENSG00000296064):​n.263T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,780 control chromosomes in the GnomAD database, including 22,621 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22619 hom., cov: 30)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: ENSG00000296064 ENST00000735999.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 9 publications found

Genes affected

ENSG00000296064 (HGNC:):

CR1 (HGNC:2334): (complement C3b/C4b receptor 1 (Knops blood group)) This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. The genome is polymorphic at this locus with allele-specific splice variants encoding different isoforms, based on the presence/absence of long homologous repeats (LHRs). The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in this gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus, sarcoidosis and Alzheimer's disease. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. [provided by RefSeq, May 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000735999.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.*2435A>G		downstream_gene	N/A	NP_000642.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296064	ENST00000735999.1		n.263T>C		non_coding_transcript_exon	Exon 2 of 2
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.*2435A>G		downstream_gene	N/A	ENSP00000356016.4
	CR1	ENST00000400960.7	TSL:1	c.*2435A>G		downstream_gene	N/A	ENSP00000383744.2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82005 AN: 151650 Hom.: 22596 Cov.: 30

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 2 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.541 AC: 82076 AN: 151772 Hom.: 22619 Cov.: 30 AF XY: 0.538 AC XY: 39878 AN XY: 74136

African (AFR) AF: 0.628 AC: 25992 AN: 41372

American (AMR) AF: 0.412 AC: 6297 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3450 AN: 5140

South Asian (SAS) AF: 0.583 AC: 2805 AN: 4808

European-Finnish (FIN) AF: 0.490 AC: 5152 AN: 10516

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34932 AN: 67896

Other (OTH) AF: 0.528 AC: 1111 AN: 2106

Alfa AF: 0.524 Hom.: 6890

Bravo AF: 0.541

Asia WGS AF: 0.631 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.9
DANN	Benign	0.40
PhyloP100		-0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10494885; hg19: chr1-207815189; COSMIC: COSV65457033;