1-207326687-G-A

Position:

• chr1-207326687-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000574.5(CD55):​c.579-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,158,534 control chromosomes in the GnomAD database, including 246 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 0.015 (22 hom., cov: 33)
  • Exomes 𝑓: 0.019 (224 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

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=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2240/152236) while in subpopulation NFE AF= 0.0206 (1399/67996). AF 95% confidence interval is 0.0197. There are 22 homozygotes in gnomad4. There are 1107 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD55	NM_000574.5	c.579-65G>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.579-65G>A		intron_variant		1	NM_000574.5	ENSP00000356031	P2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2238 AN: 152118 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0190 AC: 19109 AN: 1006298 Hom.: 224 AF XY: 0.0183 AC XY: 9526 AN XY: 520328

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.00920

Gnomad4 ASJ exome AF: 0.00664

Gnomad4 EAS exome AF: 0.0000536

Gnomad4 SAS exome AF: 0.00367

Gnomad4 FIN exome AF: 0.0344

Gnomad4 NFE exome AF: 0.0221

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0147 AC: 2240 AN: 152236 Hom.: 22 Cov.: 33 AF XY: 0.0149 AC XY: 1107 AN XY: 74442

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0364

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0159 Hom.: 4

Bravo AF: 0.0130

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.49

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: rs28371662; hg19: chr1-207500032;