Variant 19-51225373-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001772.4(CD33):c.193G>C(p.Ala65Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,196 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 23 hom. )

Consequence

CD33
NM_001772.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.535

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:

CD33 (HGNC:):

CD33 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=0.0031920373).

BP6

Variant 19-51225373-G-C is Benign according to our data. Variant chr19-51225373-G-C is described in ClinVar as [Benign]. Clinvar id is 715382.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 = 0.00939 (1431/152318) while in subpopulation AFR AF= 0.0297 (1236/41572). AF 95% confidence interval is 0.0284. There are 18 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD33	NM_001772.4 linkuse as main transcript	c.193G>C	p.Ala65Pro	missense_variant	2/7	ENST00000262262.5	NP_001763.3	P20138-1Q546G0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD33	ENST00000262262.5 linkuse as main transcript	c.193G>C	p.Ala65Pro	missense_variant	2/7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.00931

AC:

1417

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00265

AC:

667

AN:

251460

Hom.:

AF XY:

0.00200

AC XY:

272

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00132

AC:

1934

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

882

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000413

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.00939

AC:

1431

AN:

152318

Hom.:

Cov.:

AF XY:

0.00863

AC XY:

643

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0297

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.0110

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0336

AC:

148

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00326

AC:

396

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.0

DANN

Benign

0.93

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.029

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.029

Sift

Benign

0.20

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.48

.;P

Vest4

0.11

MVP

0.54

MPC

0.18

ClinPred

0.020

GERP RS

-3.3

Varity_R

0.66

gMVP

0.49

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

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