19-51225590-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001772.4(CD33):c.410A>G(p.His137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,555,428 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 19 hom., cov: 31)

Exomes 𝑓: 0.00093 ( 17 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.03

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006160289).

BP6

Variant 19-51225590-A-G is Benign according to our data. Variant chr19-51225590-A-G is described in ClinVar as [Benign]. Clinvar id is 775425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00897 (1366/152268) while in subpopulation AFR AF = 0.0312 (1297/41534). AF 95% confidence interval is 0.0298. There are 19 homozygotes in GnomAd4. There are 630 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.410A>G	p.His137Arg	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.410A>G	p.His137Arg	missense_variant	Exon 2 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.00897

AC:

1365

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00270

AC:

547

AN:

202796

AF XY:

0.00205

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.000194

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000746

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.000934

AC:

1310

AN:

1403160

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

575

AN XY:

691414

show subpopulations

African (AFR)

AF:

0.0322

AC:

1022

AN:

31782

American (AMR)

AF:

0.00213

AC:

AN:

37996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21614

East Asian (EAS)

AF:

0.00

AC:

AN:

39266

South Asian (SAS)

AF:

0.0000525

AC:

AN:

76152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50676

Middle Eastern (MID)

AF:

0.00201

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.0000693

AC:

AN:

1082530

Other (OTH)

AF:

0.00203

AC:

117

AN:

57680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00897

AC:

1366

AN:

152268

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

630

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0312

AC:

1297

AN:

41534

American (AMR)

AF:

0.00359

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68014

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

147

221

294

368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.0102

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00277

AC:

334

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.079

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.011

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.26

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.00030

T;T

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PhyloP100

-2.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.034

Sift

Benign

0.36

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0070

.;B

Vest4

0.040

MVP

0.42

MPC

0.079

ClinPred

0.035

GERP RS

-4.6

PromoterAI

0.017

Neutral

(source)

Varity_R

0.46

gMVP

0.14

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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19-51225590-A-G

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