rs60822373

chr1-207331122-G-Cchr1-207331122-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000574.5(CD55):c.679G>C(p.Ala227Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,611,430 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: CD55 NM_000574.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.116

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067967772).
• BP6: Variant 1-207331122-G-C is Benign according to our data. Variant chr1-207331122-G-C is described in ClinVar as [Benign]. Clinvar id is 1164353.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-207331122-G-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0055 (837/152158) while in subpopulation AFR AF= 0.0183 (760/41488). AF 95% confidence interval is 0.0172. There are 8 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD55	NM_000574.5	c.679G>C	p.Ala227Pro	missense_variant	6/10	ENST00000367064.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD55	ENST00000367064.9	c.679G>C	p.Ala227Pro	missense_variant	6/10	1	NM_000574.5	P2

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 828 AN: 152040 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00164 AC: 411 AN: 250250 Hom.: 3 AF XY: 0.00112 AC XY: 151 AN XY: 135290

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000984

GnomAD4 exome AF: 0.000624 AC: 911 AN: 1459272 Hom.: 10 Cov.: 30 AF XY: 0.000565 AC XY: 410 AN XY: 725838

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000504

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00550 AC: 837 AN: 152158 Hom.: 8 Cov.: 32 AF XY: 0.00555 AC XY: 413 AN XY: 74394

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.000471 Hom.: 1

Bravo AF: 0.00629

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0195 AC: 86

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00204 AC: 248

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	17
Dann	Benign	0.72
DEOGEN2	Benign	0.099	T;.;T;.;.;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.61	T;T;T;T;T;T;T
MetaRNN	Benign	0.0068	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;.;.;N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.030	N;N;N;.;N;.;.
REVEL	Benign	0.12
Sift	Benign	0.17	T;T;T;.;T;.;.
Sift4G	Benign	0.22	T;T;T;.;T;T;.
Polyphen		1.0	D;B;D;.;B;.;.
Vest4		0.18
MVP		0.66
MPC		0.54
ClinPred		0.020	T
GERP RS		2.0
Varity_R		0.22
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs60822373; hg19: chr1-207504467;