Variant 19-51225385-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001772.4(CD33):c.205A>G(p.Arg69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,613,862 control chromosomes in the GnomAD database, including 134,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.41 ( 13708 hom., cov: 31)

Exomes 𝑓: 0.40 ( 120883 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.05

Variant links:

Genes affected

CD33 (HGNC:1659): (CD33 molecule) Enables protein phosphatase binding activity and sialic acid binding activity. Involved in several processes, including negative regulation of cytokine production; negative regulation of monocyte activation; and positive regulation of protein tyrosine phosphatase activity. Located in several cellular components, including Golgi apparatus; external side of plasma membrane; and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

CD33 links:

LOC107985327 (HGNC:):

LOC107985327 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4838576E-4).

BP6

Variant 19-51225385-A-G is Benign according to our data. Variant chr19-51225385-A-G is described in ClinVar as [Benign]. Clinvar id is 1225488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.205A>G	p.Arg69Gly	missense_variant	Exon 2 of 7	ENST00000262262.5	NP_001763.3	P20138-1Q546G0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD33	ENST00000262262.5 link	c.205A>G	p.Arg69Gly	missense_variant	Exon 2 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62996

AN:

151928

Hom.:

13695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.0852

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.349

AC:

87652

AN:

251434

Hom.:

17236

AF XY:

0.351

AC XY:

47678

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.507

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.0806

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.398

AC:

581802

AN:

1461816

Hom.:

120883

Cov.:

AF XY:

0.395

AC XY:

287313

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.0606

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.415

AC:

63034

AN:

152046

Hom.:

13708

Cov.:

AF XY:

0.405

AC XY:

30132

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.0842

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.396

Hom.:

6282

Bravo

AF:

0.416

TwinsUK

AF:

0.439

AC:

1627

ALSPAC

AF:

0.414

AC:

1596

ESP6500AA

AF:

0.502

AC:

2210

ESP6500EA

AF:

0.430

AC:

3698

ExAC

AF:

0.358

AC:

43419

Asia WGS

AF:

0.195

AC:

678

AN:

3478

EpiCase

AF:

0.427

EpiControl

AF:

0.436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30917570) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.043

DANN

Benign

0.27

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.0025

T;T

MetaRNN

Benign

0.00015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.037

Sift

Benign

0.33

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

.;B

Vest4

0.070

MPC

0.082

ClinPred

0.018

GERP RS

-7.0

Varity_R

0.48

gMVP

0.17

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