chr1-207607240-C-A

Variant names:

• chr1-207607240-C-A
• rs115988205
• NM_000651.6:c.5811-11C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_000651.6(CR1):​c.5811-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,605,718 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (57 hom.)
• Consequence: CR1 NM_000651.6 intron
• Scores: Splicing: ADA: 0.004023
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0990
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-207607240-C-A is Benign according to our data. Variant chr1-207607240-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 445843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 BG gene

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.5811-11C>A		intron	N/A	NP_000642.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR1	ENST00000367049.9	TSL:5 MANE Select	c.5811-11C>A		intron	N/A	ENSP00000356016.4	E9PDY4
	CR1	ENST00000400960.7	TSL:1	c.4461-11C>A		intron	N/A	ENSP00000383744.2	P17927
	CR1	ENST00000367051.6	TSL:5	c.4461-11C>A		intron	N/A	ENSP00000356018.1	P17927

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152108 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.00950

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00617 AC: 1536 AN: 248950 AF XY: 0.00620

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.00906

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.00850

Gnomad OTH exome AF: 0.00696

GnomAD4 exome AF: 0.00757 AC: 10999 AN: 1453492 Hom.: 57 Cov.: 29 AF XY: 0.00749 AC XY: 5419 AN XY: 723646

African (AFR) AF: 0.00141 AC: 47 AN: 33296

American (AMR) AF: 0.00889 AC: 397 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 315 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.000918 AC: 79 AN: 86060

European-Finnish (FIN) AF: 0.00142 AC: 76 AN: 53392

Middle Eastern (MID) AF: 0.00854 AC: 49 AN: 5736

European-Non Finnish (NFE) AF: 0.00866 AC: 9569 AN: 1104536

Other (OTH) AF: 0.00777 AC: 467 AN: 60132

GnomAD4 genome AF: 0.00612 AC: 931 AN: 152226 Hom.: 6 Cov.: 32 AF XY: 0.00556 AC XY: 414 AN XY: 74420

African (AFR) AF: 0.00168 AC: 70 AN: 41560

American (AMR) AF: 0.00949 AC: 145 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10590

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 67986

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00784 Hom.: 3

Bravo AF: 0.00740

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	KNOPS BLOOD GROUP SYSTEM;C1970028:Malaria, susceptibility to (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.80
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0040
dbscSNV1_RF	Benign	0.078
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: rs115988205; hg19: chr1-207780585;