rs12066318

chr1-207362286-T-C

Variant summary

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

The ENST00000695826.1(CD55):c.1082-10483T>C 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 152,062 control chromosomes in the GnomAD database, including 11,709 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 (11709 hom., cov: 31)
• Consequence: CD55 ENST00000695826.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973

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=-0.9).
• 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000618707.2	c.586-5084T>C		intron_variant
CD55	ENST00000695826.1	c.1082-10483T>C		intron_variant				A2
CD55	ENST00000634386.1	c.167+22869T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57396 AN: 151944 Hom.: 11695 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: 0.381

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: 57434 AN: 152062 Hom.: 11709 Cov.: 31 AF XY: 0.378 AC XY: 28115 AN XY: 74312

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.438

Alfa AF: 0.404 Hom.: 1619

Bravo AF: 0.373

Asia WGS AF: 0.329 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.6
Dann	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12066318; hg19: chr1-207535631;