chr19-51235662-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001772.4(CD33):c.910G>A(p.Gly304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,898 control chromosomes in the GnomAD database, including 31,505 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1997 hom., cov: 31)

Exomes 𝑓: 0.19 ( 29508 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.577

Publications

43 publications found

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:

ENSG00000268595 (HGNC:):

ENSG00000268595 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 19-51235662-G-A is Benign according to our data. Variant chr19-51235662-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.910G>A	p.Gly304Arg	missense_variant	Exon 6 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.910G>A	p.Gly304Arg	missense_variant	Exon 6 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21505

AN:

151980

Hom.:

1997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0431

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.142

GnomAD2 exomes

AF:

0.147

AC:

36548

AN:

248748

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.0772

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.190

AC:

277033

AN:

1460800

Hom.:

29508

Cov.:

AF XY:

0.185

AC XY:

134774

AN XY:

726622

show subpopulations

African (AFR)

AF:

0.0405

AC:

1357

AN:

33476

American (AMR)

AF:

0.0815

AC:

3638

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3696

AN:

26106

East Asian (EAS)

AF:

0.000202

AC:

AN:

39688

South Asian (SAS)

AF:

0.0491

AC:

4222

AN:

86052

European-Finnish (FIN)

AF:

0.262

AC:

13996

AN:

53326

Middle Eastern (MID)

AF:

0.106

AC:

611

AN:

5766

European-Non Finnish (NFE)

AF:

0.216

AC:

239816

AN:

1111396

Other (OTH)

AF:

0.161

AC:

9689

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

11298

22596

33895

45193

56491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8072

16144

24216

32288

40360

<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:

0.141

AC:

21498

AN:

152098

Hom.:

1997

Cov.:

AF XY:

0.141

AC XY:

10460

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0464

AC:

1925

AN:

41516

American (AMR)

AF:

0.105

AC:

1612

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3472

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.0438

AC:

211

AN:

4818

European-Finnish (FIN)

AF:

0.261

AC:

2754

AN:

10556

Middle Eastern (MID)

AF:

0.137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.207

AC:

14083

AN:

67956

Other (OTH)

AF:

0.140

AC:

295

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

879

1757

2636

3514

4393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.174

Hom.:

6712

Bravo

AF:

0.128

TwinsUK

AF:

0.222

AC:

822

ALSPAC

AF:

0.229

AC:

883

ESP6500AA

AF:

0.0542

AC:

239

ESP6500EA

AF:

0.198

AC:

1704

ExAC

AF:

0.148

AC:

17960

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23444229) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.6

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.11

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0093

LIST_S2

Benign

0.44

T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L;L

PhyloP100

-0.58

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.14

T;D;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.14

.;.;.;B

Vest4

0.024

MutPred

0.12

.;.;Gain of MoRF binding (P = 0.0143);Gain of MoRF binding (P = 0.0143);

MPC

0.077

ClinPred

0.0028

GERP RS

0.28

Varity_R

0.061

gMVP

0.093

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over