dbSNP rs28371667: CD55:n.946C>T (chr1-207337170-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000465534.5(CD55):n.946C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 620,816 control chromosomes in the GnomAD database, including 98 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 0.014 ( 26 hom., cov: 32)

Exomes 𝑓: 0.016 ( 72 hom. )

Consequence

CD55
ENST00000465534.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.267

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038772523).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0135 (2062/152278) while in subpopulation NFE AF = 0.0201 (1366/68004). AF 95% confidence interval is 0.0192. There are 26 homozygotes in GnomAd4. There are 953 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5 link	c.980-159C>T		intron_variant	Intron 7 of 9	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.980-159C>T		intron_variant	Intron 7 of 9	1	NM_000574.5	ENSP00000356031.4		P08174-1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2062

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.0162

AC:

7575

AN:

468538

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

3838

AN XY:

249108

show subpopulations

African (AFR)

AF:

0.00387

AC:

AN:

12648

American (AMR)

AF:

0.00891

AC:

165

AN:

18520

Ashkenazi Jewish (ASJ)

AF:

0.0217

AC:

298

AN:

13754

East Asian (EAS)

AF:

0.00

AC:

AN:

31506

South Asian (SAS)

AF:

0.00209

AC:

AN:

46912

European-Finnish (FIN)

AF:

0.0304

AC:

1080

AN:

35574

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

3624

European-Non Finnish (NFE)

AF:

0.0194

AC:

5405

AN:

279240

Other (OTH)

AF:

0.0170

AC:

455

AN:

26760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

368

736

1103

1471

1839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.0135

AC:

2062

AN:

152278

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

953

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00390

AC:

162

AN:

41572

American (AMR)

AF:

0.0107

AC:

163

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00187

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0239

AC:

254

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0201

AC:

1366

AN:

68004

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0148

Hom.:

Bravo

AF:

0.0123

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0187

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.6

(source)

DANN

Benign

0.70

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0039

PhyloP100

0.27

Sift4G

Benign

0.47

Vest4

0.086

MVP

0.67

GERP RS

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over