dbSNP rs35112940: CD33:p.Gly304Arg (chr19-51235662-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -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. 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 0.14 ( 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

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 -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 id 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

GnomAD3 exomes

AF:

0.147

AC:

36548

AN:

248748

Hom.:

3715

AF XY:

0.147

AC XY:

19825

AN XY:

134486

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 SAS exome

AF:

0.0465

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

Gnomad4 AFR exome

AF:

0.0405

Gnomad4 AMR exome

AF:

0.0815

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0491

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.141

AC:

21498

AN:

152098

Hom.:

1997

Cov.:

AF XY:

0.141

AC XY:

10460

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0438

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.186

Hom.:

4835

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

Mar 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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

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

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

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