chr1-207324466-A-G

Position:

• chr1-207324466-A-G

Variant summary

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

The NM_000574.5(CD55):​c.287-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 747,162 control chromosomes in the GnomAD database, including 390 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 0.041 (195 hom., cov: 32)
  • Exomes 𝑓: 0.021 (195 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5	c.287-93A>G		intron_variant		ENST00000367064.9	NP_000565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9	c.287-93A>G		intron_variant		1	NM_000574.5	ENSP00000356031	P2

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6227 AN: 152172 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0210 AC: 12510 AN: 594872 Hom.: 195 AF XY: 0.0200 AC XY: 6140 AN XY: 306560

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.00670

Gnomad4 EAS exome AF: 0.0000967

Gnomad4 SAS exome AF: 0.00385

Gnomad4 FIN exome AF: 0.0348

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.0409 AC: 6235 AN: 152290 Hom.: 195 Cov.: 32 AF XY: 0.0402 AC XY: 2992 AN XY: 74458

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0353 Hom.: 30

Bravo AF: 0.0439

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
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: rs28371601; hg19: chr1-207497811;