Variant rs17645 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001803.3(CD52):c.123A>G(p.Ile41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,612,100 control chromosomes in the GnomAD database, including 428,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.70 ( 37062 hom., cov: 31)

Exomes 𝑓: 0.73 ( 390988 hom. )

Consequence

CD52
NM_001803.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0940

Variant links:

Genes affected

CD52 (HGNC:1804): (CD52 molecule) Involved in positive regulation of cytosolic calcium ion concentration. Predicted to be located in extracellular region and plasma membrane. Predicted to be intrinsic component of plasma membrane. Predicted to be active in sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

CD52 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0592913E-6).

BP6

Variant 1-26320239-A-G is Benign according to our data. Variant chr1-26320239-A-G is described in ClinVar as [Benign]. Clinvar id is 3059585.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD52	NM_001803.3 linkuse as main transcript	c.123A>G	p.Ile41Met	missense_variant	2/2	ENST00000374213.3	NP_001794.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD52	ENST00000374213.3 linkuse as main transcript	c.123A>G	p.Ile41Met	missense_variant	2/2	1	NM_001803.3	ENSP00000363330	P1
CD52	ENST00000470468.1 linkuse as main transcript	n.296A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105278

AN:

151436

Hom.:

37033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.663

Gnomad NFE

AF:

0.755

Gnomad OTH

AF:

0.698

GnomAD3 exomes

AF:

0.669

AC:

167193

AN:

249970

Hom.:

57557

AF XY:

0.671

AC XY:

90753

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.657

Gnomad AMR exome

AF:

0.574

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.424

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.704

Gnomad NFE exome

AF:

0.756

Gnomad OTH exome

AF:

0.705

GnomAD4 exome

AF:

0.727

AC:

1061486

AN:

1460546

Hom.:

390988

Cov.:

AF XY:

0.723

AC XY:

524997

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.659

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.545

Gnomad4 FIN exome

AF:

0.709

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.700

GnomAD4 genome

AF:

0.695

AC:

105356

AN:

151554

Hom.:

37062

Cov.:

AF XY:

0.687

AC XY:

50871

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.648

Gnomad4 ASJ

AF:

0.769

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.691

Alfa

AF:

0.739

Hom.:

83858

Bravo

AF:

0.693

TwinsUK

AF:

0.766

AC:

2842

ALSPAC

AF:

0.758

AC:

2920

ESP6500AA

AF:

0.667

AC:

2938

ESP6500EA

AF:

0.765

AC:

6583

ExAC

AF:

0.671

AC:

81469

Asia WGS

AF:

0.459

AC:

1598

AN:

3476

EpiCase

AF:

0.758

EpiControl

AF:

0.759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD52-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

DANN

Benign

0.32

DEOGEN2

Benign

0.039

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0000041

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.68

REVEL

Benign

0.073

Sift

Benign

0.29

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.085

MPC

0.23

ClinPred

0.0027

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.056

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over