rs7544288

Positions:

• chr1-207335677-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000574.5(CD55):​c.854-1016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,828 control chromosomes in the GnomAD database, including 11,712 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 0.38 (11712 hom., cov: 31)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5	c.854-1016G>A		intron_variant		ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.854-1016G>A		intron_variant		1	NM_000574.5	ENSP00000356031	P2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57355 AN: 151710 Hom.: 11698 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.378 AC: 57393 AN: 151828 Hom.: 11712 Cov.: 31 AF XY: 0.379 AC XY: 28103 AN XY: 74176

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.437

Alfa AF: 0.434 Hom.: 24540

Bravo AF: 0.373

Asia WGS AF: 0.332 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.73

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: rs7544288; hg19: chr1-207509022;