Genetic Variant CD55:c.287-93A>G (chr1-207324466-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.540

Publications

1 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: Orphanet, Labcorp Genetics (formerly Invitae)

CD55 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000574.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD55	NM_000574.5	MANE Select	c.287-93A>G	intron	N/A	NP_000565.1	P08174-1
CD55	NM_001300902.2		c.287-93A>G	intron	N/A	NP_001287831.1	B1AP13
CD55	NM_001114752.3		c.287-93A>G	intron	N/A	NP_001108224.1	P08174-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD55	ENST00000367064.9	TSL:1 MANE Select	c.287-93A>G	intron	N/A	ENSP00000356031.4	P08174-1
CD55	ENST00000367063.6	TSL:1	c.287-93A>G	intron	N/A	ENSP00000356030.2	B1AP13
CD55	ENST00000314754.12	TSL:1	c.287-93A>G	intron	N/A	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6227

AN:

152172

Hom.:

195

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0932

AC:

1361

AN:

14604

American (AMR)

AF:

0.0183

AC:

347

AN:

18940

Ashkenazi Jewish (ASJ)

AF:

0.00670

AC:

AN:

14320

East Asian (EAS)

AF:

0.0000967

AC:

AN:

31026

South Asian (SAS)

AF:

0.00385

AC:

149

AN:

38660

European-Finnish (FIN)

AF:

0.0348

AC:

1450

AN:

41702

Middle Eastern (MID)

AF:

0.0177

AC:

AN:

2368

European-Non Finnish (NFE)

AF:

0.0206

AC:

8297

AN:

403162

Other (OTH)

AF:

0.0254

AC:

765

AN:

30090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

606

1213

1819

2426

3032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.0409

AC:

6235

AN:

152290

Hom.:

195

Cov.:

AF XY:

0.0402

AC XY:

2992

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0938

AC:

3895

AN:

41528

American (AMR)

AF:

0.0253

AC:

387

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00331

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0363

AC:

386

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0210

AC:

1431

AN:

68028

Other (OTH)

AF:

0.0360

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

289

578

868

1157

1446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0502

Hom.:

123

Bravo

AF:

0.0439

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.6

(source)

DANN

Benign

0.73

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over