rs2184476

Positions:

• chr1-207331324-G-A
• chr1-207331324-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CD55	NM_000574.5	c.853+28G>A		intron_variant		ENST00000367064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.853+28G>A		intron_variant		1	NM_000574.5	P2

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

GnomAD3 exomes AF: 0.669 AC: 164655 AN: 246148 Hom.: 56284 AF XY: 0.670 AC XY: 89309 AN XY: 133372

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 SAS exome AF: 0.591

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

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.746

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.692

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

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.731

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2184476; hg19: chr1-207504669; COSMIC: COSV58577130;