Genetic Variant CD55:c.579-65G>A (chr1-207326687-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.804

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:

Genome browser will be placed here

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=-0.78).

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

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.579-65G>A	intron	N/A	NP_000565.1	P08174-1
CD55	NM_001300902.2		c.579-65G>A	intron	N/A	NP_001287831.1	B1AP13
CD55	NM_001114752.3		c.579-65G>A	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.579-65G>A	intron	N/A	ENSP00000356031.4	P08174-1
CD55	ENST00000367063.6	TSL:1	c.579-65G>A	intron	N/A	ENSP00000356030.2	B1AP13
CD55	ENST00000314754.12	TSL:1	c.579-65G>A	intron	N/A	ENSP00000316333.8	P08174-2

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2238

AN:

152118

Hom.:

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.00357

AC:

AN:

24102

American (AMR)

AF:

0.00920

AC:

387

AN:

42062

Ashkenazi Jewish (ASJ)

AF:

0.00664

AC:

151

AN:

22748

East Asian (EAS)

AF:

0.0000536

AC:

AN:

37312

South Asian (SAS)

AF:

0.00367

AC:

276

AN:

75252

European-Finnish (FIN)

AF:

0.0344

AC:

1807

AN:

52472

Middle Eastern (MID)

AF:

0.0307

AC:

150

AN:

4884

European-Non Finnish (NFE)

AF:

0.0221

AC:

15511

AN:

702404

Other (OTH)

AF:

0.0164

AC:

739

AN:

45062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

905

1810

2714

3619

4524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.0147

AC:

2240

AN:

152236

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1107

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00344

AC:

143

AN:

41534

American (AMR)

AF:

0.0145

AC:

222

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00249

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0364

AC:

386

AN:

10606

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0206

AC:

1399

AN:

67996

Other (OTH)

AF:

0.0166

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0126

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.49

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism

(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