rs6662070

Variant names:

• chr1-207332364-A-G
• rs6662070
• NM_000574.5:c.853+1068A>G

Variant summary

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

The NM_000574.5(CD55):​c.853+1068A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,970 control chromosomes in the GnomAD database, including 37,303 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 0.70 (37303 hom., cov: 32)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784
• Publications: 11 publications found

Genes affected

CD55 (HGNC:2665): (CD55 molecule (Cromer blood group)) This gene encodes a glycoprotein involved in the regulation of the complement cascade. Binding of the encoded protein to complement proteins accelerates their decay, thereby disrupting the cascade and preventing damage to host cells. Antigens present on this protein constitute the Cromer blood group system (CROM). Alternative splicing results in multiple transcript variants. The predominant transcript variant encodes a membrane-bound protein, but alternatively spliced transcripts may produce soluble proteins. [provided by RefSeq, Jul 2014]

CD55 Gene-Disease associations (from GenCC):

• protein-losing enteropathy

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000574.5. 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
	CD55	NM_000574.5	MANE Select	c.853+1068A>G		intron	N/A	NP_000565.1	P08174-1
	CD55	NM_001300902.2		c.853+1068A>G		intron	N/A	NP_001287831.1	B1AP13
	CD55	NM_001114752.3		c.853+1068A>G		intron	N/A	NP_001108224.1	P08174-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD55	ENST00000367064.9	TSL:1 MANE Select	c.853+1068A>G		intron	N/A	ENSP00000356031.4	P08174-1
	CD55	ENST00000367063.6	TSL:1	c.853+1068A>G		intron	N/A	ENSP00000356030.2	B1AP13
	CD55	ENST00000314754.12	TSL:1	c.853+1068A>G		intron	N/A	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105729 AN: 151852 Hom.: 37271 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.736

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105820 AN: 151970 Hom.: 37303 Cov.: 32 AF XY: 0.693 AC XY: 51445 AN XY: 74258

African (AFR) AF: 0.698 AC: 28940 AN: 41454

American (AMR) AF: 0.697 AC: 10654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2983 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2201 AN: 5174

South Asian (SAS) AF: 0.573 AC: 2766 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7925 AN: 10542

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47813 AN: 67916

Other (OTH) AF: 0.735 AC: 1551 AN: 2110

Alfa AF: 0.698 Hom.: 14054

Bravo AF: 0.695

Asia WGS AF: 0.479 AC: 1662 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.86
PhyloP100		-0.78
Mutation Taster		=100/0	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: rs6662070; hg19: chr1-207505709;