Variant 19-51225847-CCCGG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001772.4(CD33):c.466_469delGGCC(p.Gly156fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,994 control chromosomes in the GnomAD database, including 576 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.016 ( 25 hom., cov: 31)

Exomes 𝑓: 0.025 ( 551 hom. )

Consequence

CD33
NM_001772.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.86

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-51225847-CCCGG-C is Benign according to our data. Variant chr19-51225847-CCCGG-C is described in ClinVar as [Benign]. Clinvar id is 3024703.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0158 (2412/152196) while in subpopulation NFE AF= 0.026 (1770/68012). AF 95% confidence interval is 0.025. There are 25 homozygotes in gnomad4. There are 1043 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD33	NM_001772.4 linkuse as main transcript	c.466_469delGGCC	p.Gly156fs	frameshift_variant	3/7	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.466_469delGGCC	p.Gly156fs	frameshift_variant	3/7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2413

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00558

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0142

AC:

3561

AN:

251316

Hom.:

AF XY:

0.0138

AC XY:

1874

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0245

AC:

35851

AN:

1461798

Hom.:

551

AF XY:

0.0236

AC XY:

17169

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00332

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.00122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.0300

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.0158

AC:

2412

AN:

152196

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00557

Gnomad4 AMR

AF:

0.0191

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00329

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00516

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0226

EpiControl

AF:

0.0242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CD33-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 17, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

CD33: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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