dbSNP rs1803254: CD33:c.*201G>C (chr19-51239889-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001772.4(CD33):c.*201G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 433,648 control chromosomes in the GnomAD database, including 5,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3114 hom., cov: 32)

Exomes 𝑓: 0.10 ( 2459 hom. )

Consequence

CD33
NM_001772.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.152

Publications

21 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 (BayesDel_noAF=-0.9).

BP6

Variant 19-51239889-G-C is Benign according to our data. Variant chr19-51239889-G-C is described in ClinVar as Benign. ClinVar VariationId is 1282621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	NM_001772.4 link	c.*201G>C		3_prime_UTR_variant	Exon 7 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.*201G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001772.4	ENSP00000262262.3		P20138-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24626

AN:

152010

Hom.:

3101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0709

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.104

AC:

29347

AN:

281518

Hom.:

2459

Cov.:

AF XY:

0.102

AC XY:

14816

AN XY:

145642

show subpopulations

African (AFR)

AF:

0.269

AC:

2031

AN:

7564

American (AMR)

AF:

0.385

AC:

3143

AN:

8158

Ashkenazi Jewish (ASJ)

AF:

0.0739

AC:

724

AN:

9794

East Asian (EAS)

AF:

0.277

AC:

5888

AN:

21280

South Asian (SAS)

AF:

0.0951

AC:

1451

AN:

15252

European-Finnish (FIN)

AF:

0.0594

AC:

1314

AN:

22116

Middle Eastern (MID)

AF:

0.0749

AC:

104

AN:

1388

European-Non Finnish (NFE)

AF:

0.0704

AC:

12531

AN:

177982

Other (OTH)

AF:

0.120

AC:

2161

AN:

17984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1147

2293

3440

4586

5733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.162

AC:

24687

AN:

152130

Hom.:

3114

Cov.:

AF XY:

0.164

AC XY:

12185

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.277

AC:

11489

AN:

41464

American (AMR)

AF:

0.328

AC:

5010

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0660

AC:

229

AN:

3472

East Asian (EAS)

AF:

0.321

AC:

1658

AN:

5170

South Asian (SAS)

AF:

0.103

AC:

498

AN:

4820

European-Finnish (FIN)

AF:

0.0578

AC:

613

AN:

10610

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0709

AC:

4821

AN:

67990

Other (OTH)

AF:

0.146

AC:

309

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

962

1924

2886

3848

4810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0495

Hom.:

Bravo

AF:

0.190

Asia WGS

AF:

0.215

AC:

748

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.73

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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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