rs60822373

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 10 hom. )

Consequence

CD55
NM_000574.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.116

Publications

10 publications found

Variant links:

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]

CD55 Gene-Disease associations (from GenCC):

protein-losing enteropathy
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

CD55 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 1164353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5 link	c.679G>C	p.Ala227Pro	missense_variant	Exon 6 of 10	ENST00000367064.9	NP_000565.1	P08174-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD55	ENST00000367064.9 link	c.679G>C	p.Ala227Pro	missense_variant	Exon 6 of 10	1	NM_000574.5	ENSP00000356031.4		P08174-1

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

828

AN:

152040

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00164

AC:

411

AN:

250250

AF XY:

0.00112

show subpopulations

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 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.:

Cov.:

AF XY:

0.000565

AC XY:

410

AN XY:

725838

show subpopulations

African (AFR)

AF:

0.0184

AC:

614

AN:

33410

American (AMR)

AF:

0.00171

AC:

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.0000467

AC:

AN:

85718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00504

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1110546

Other (OTH)

AF:

0.00144

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00550

AC:

837

AN:

152158

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0183

AC:

760

AN:

41488

American (AMR)

AF:

0.00320

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68008

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000471

Hom.:

Bravo

AF:

0.00629

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00204

AC:

248

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.099

T;.;T;.;.;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.064

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

MutationAssessor

Benign

-1.3

N;.;.;N;N;.;N

PhyloP100

0.12

PrimateAI

Benign

0.24

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

GERP RS

2.0

Varity_R

0.22

gMVP

0.56

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over