rs10746463

chr1-207337251-G-Achr1-207337251-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.980-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 932,012 control chromosomes in the GnomAD database, including 221,753 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 (36896 hom., cov: 32)
  • Exomes 𝑓: 0.68 (184857 hom.)
• Consequence: CD55 NM_000574.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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 (MetaRNN=0.0030991137).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD55	NM_000574.5	c.980-78G>A		intron_variant		ENST00000367064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.980-78G>A		intron_variant		1	NM_000574.5	P2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105163 AN: 151934 Hom.: 36862 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.732

GnomAD4 exome AF: 0.684 AC: 533855 AN: 779960 Hom.: 184857 Cov.: 10 AF XY: 0.682 AC XY: 281202 AN XY: 412116

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.669

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.692 AC: 105256 AN: 152052 Hom.: 36896 Cov.: 32 AF XY: 0.689 AC XY: 51201 AN XY: 74316

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.731

Alfa AF: 0.625 Hom.: 2242

Bravo AF: 0.689

TwinsUK AF: 0.685 AC: 2541

ALSPAC AF: 0.682 AC: 2629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.080
Dann	Benign	0.59
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0031	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
Sift4G	Benign	0.13	T
Vest4		0.10
MVP		0.57
GERP RS		-6.8

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: rs10746463; hg19: chr1-207510596; COSMIC: COSV58577134; COSMIC: COSV58577134;