1-207331324-G-A

Variant names:

• chr1-207331324-G-A
• rs2184476
• NM_000574.5:c.853+28G>A

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+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,588,398 control chromosomes in the GnomAD database, including 378,001 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 0.69 (36862 hom., cov: 31)
  • Exomes 𝑓: 0.69 (341139 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5	c.853+28G>A		intron_variant	Intron 6 of 9	ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.853+28G>A		intron_variant	Intron 6 of 9	1	NM_000574.5	ENSP00000356031.4

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105093 AN: 151856 Hom.: 36828 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.732

GnomAD2 exomes AF: 0.669 AC: 164655 AN: 246148 AF XY: 0.670

Gnomad AFR exome AF: 0.680

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.856

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.686 AC: 985817 AN: 1436424 Hom.: 341139 Cov.: 25 AF XY: 0.685 AC XY: 490563 AN XY: 715844

African (AFR) AF: 0.675 AC: 22079 AN: 32686

American (AMR) AF: 0.662 AC: 28443 AN: 42952

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22095 AN: 25780

East Asian (EAS) AF: 0.498 AC: 19662 AN: 39494

South Asian (SAS) AF: 0.591 AC: 49830 AN: 84374

European-Finnish (FIN) AF: 0.746 AC: 39751 AN: 53264

Middle Eastern (MID) AF: 0.807 AC: 4608 AN: 5708

European-Non Finnish (NFE) AF: 0.694 AC: 758121 AN: 1092624

Other (OTH) AF: 0.692 AC: 41228 AN: 59542

GnomAD4 genome AF: 0.692 AC: 105186 AN: 151974 Hom.: 36862 Cov.: 31 AF XY: 0.689 AC XY: 51137 AN XY: 74254

African (AFR) AF: 0.684 AC: 28333 AN: 41440

American (AMR) AF: 0.697 AC: 10637 AN: 15272

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

East Asian (EAS) AF: 0.425 AC: 2196 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2766 AN: 4822

European-Finnish (FIN) AF: 0.751 AC: 7914 AN: 10538

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

European-Non Finnish (NFE) AF: 0.704 AC: 47827 AN: 67944

Other (OTH) AF: 0.731 AC: 1543 AN: 2112

Alfa AF: 0.694 Hom.: 4793

Bravo AF: 0.693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		-0.0010
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: rs2184476; hg19: chr1-207504669; COSMIC: COSV58577130;