Genetic Variant ENST00000465534.5:n.979A>G (chr1-207337203-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 ENST00000465534.5(CD55):n.979A>G 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 0.688 in 686,688 control chromosomes in the GnomAD database, including 164,550 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 0.69 ( 36889 hom., cov: 32)

Exomes 𝑓: 0.69 ( 127661 hom. )

Consequence

CD55
ENST00000465534.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

15 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=0.0028584003).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD55	NM_000574.5 link	c.980-126A>G		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.980-126A>G		intron_variant	Intron 7 of 9	1	NM_000574.5	ENSP00000356031.4		P08174-1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105149

AN:

151924

Hom.:

36855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.696

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.704

Gnomad OTH

AF:

0.732

GnomAD4 exome

AF:

0.686

AC:

367033

AN:

534646

Hom.:

127661

Cov.:

AF XY:

0.683

AC XY:

195495

AN XY:

286250

show subpopulations

African (AFR)

AF:

0.680

AC:

9901

AN:

14562

American (AMR)

AF:

0.675

AC:

17619

AN:

26118

Ashkenazi Jewish (ASJ)

AF:

0.861

AC:

13075

AN:

15192

East Asian (EAS)

AF:

0.513

AC:

17161

AN:

33460

South Asian (SAS)

AF:

0.595

AC:

31678

AN:

53260

European-Finnish (FIN)

AF:

0.748

AC:

31761

AN:

42476

Middle Eastern (MID)

AF:

0.810

AC:

3051

AN:

3768

European-Non Finnish (NFE)

AF:

0.702

AC:

222129

AN:

316488

Other (OTH)

AF:

0.705

AC:

20658

AN:

29322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5719

11439

17158

22878

28597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1334

2668

4002

5336

6670

<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:

0.692

AC:

105242

AN:

152042

Hom.:

36889

Cov.:

AF XY:

0.689

AC XY:

51187

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.684

AC:

28349

AN:

41452

American (AMR)

AF:

0.696

AC:

10620

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

2984

AN:

3472

East Asian (EAS)

AF:

0.425

AC:

2198

AN:

5174

South Asian (SAS)

AF:

0.573

AC:

2760

AN:

4814

European-Finnish (FIN)

AF:

0.752

AC:

7970

AN:

10592

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.704

AC:

47833

AN:

67962

Other (OTH)

AF:

0.731

AC:

1541

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1643

3287

4930

6574

8217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.691

Hom.:

13814

Bravo

AF:

0.690

TwinsUK

AF:

0.685

AC:

2540

ALSPAC

AF:

0.682

AC:

2627

Asia WGS

AF:

0.477

AC:

1665

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.76

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0029

PhyloP100

-1.1

Sift4G

Benign

0.94

Vest4

0.021

MVP

0.59

GERP RS

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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