rs3738467

Variant names:

• chr1-207552816-G-A
• rs3738467
• NM_000651.6:c.3066G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-207552816-G-A
• chr1-207552816-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_000651.6(CR1):​c.3066G>A​(p.Gln1022Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.000012 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CR1 NM_000651.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 13 publications found

Genes affected

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]

CR1-AS1 (HGNC:40160):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.459 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000651.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	NM_000651.6	MANE Select	c.3066G>A	p.Gln1022Gln	synonymous	Exon 19 of 47	NP_000642.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.3066G>A	p.Gln1022Gln	synonymous	Exon 19 of 47	ENSP00000356016.4	E9PDY4
	CR1	ENST00000400960.7	TSL:1	c.2236+10236G>A		intron	N/A	ENSP00000383744.2	P17927
	CR1	ENST00000367050.8	TSL:1	n.1837G>A		non_coding_transcript_exon	Exon 11 of 13

Frequencies

GnomAD3 genomes AF: 0.0000115 AC: 1 AN: 86614 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.0000408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000107 AC: 1 AN: 935400 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 477500

African (AFR) AF: 0.00 AC: 0 AN: 25462

American (AMR) AF: 0.00 AC: 0 AN: 36070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21224

East Asian (EAS) AF: 0.00 AC: 0 AN: 24960

South Asian (SAS) AF: 0.00 AC: 0 AN: 73508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3366

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 661932

Other (OTH) AF: 0.0000239 AC: 1 AN: 41922

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000115 AC: 1 AN: 86614 Hom.: 0 Cov.: 11 AF XY: 0.0000241 AC XY: 1 AN XY: 41462

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000408 AC: 1 AN: 24530

American (AMR) AF: 0.00 AC: 0 AN: 8518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2288

East Asian (EAS) AF: 0.00 AC: 0 AN: 1416

South Asian (SAS) AF: 0.00 AC: 0 AN: 1868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40886

Other (OTH) AF: 0.00 AC: 0 AN: 962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.81
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs3738467; hg19: chr1-207726161;