Variant 19-51225219-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001772.4(CD33):c.39G>A(p.Gly13=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000803 in 1,613,328 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 6 hom. )

Consequence

CD33
NM_001772.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00006033

Clinical Significance

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

Conservation

PhyloP100: -0.926

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-51225219-G-A is Benign according to our data. Variant chr19-51225219-G-A is described in ClinVar as [Benign]. Clinvar id is 717093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.926 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000446 (651/1461012) while in subpopulation AFR AF= 0.0163 (547/33462). AF 95% confidence interval is 0.0152. There are 6 homozygotes in gnomad4_exome. There are 262 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD33	NM_001772.4 linkuse as main transcript	c.39G>A	p.Gly13=	splice_region_variant, synonymous_variant	2/7	ENST00000262262.5	NP_001763.3
LOC107985327	XR_007067309.1 linkuse as main transcript	n.232-30559C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD33	ENST00000262262.5 linkuse as main transcript	c.39G>A	p.Gly13=	splice_region_variant, synonymous_variant	2/7	1	NM_001772.4	ENSP00000262262	P2	P20138-1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

250394

Hom.:

AF XY:

0.000850

AC XY:

115

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000446

AC:

651

AN:

1461012

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

262

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152316

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00468

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.0020

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

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