rs2455069

chr19-51225385-A-Gchr19-51225385-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001772.4(CD33):c.205A>G(p.Arg69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,613,862 control chromosomes in the GnomAD database, including 134,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.41 (13708 hom., cov: 31)
  • Exomes 𝑓: 0.40 (120883 hom.)
• Consequence: CD33 NM_001772.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.05

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]

LOC107985327 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4838576E-4).
• BP6: Variant 19-51225385-A-G is Benign according to our data. Variant chr19-51225385-A-G is described in ClinVar as [Benign]. Clinvar id is 1225488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD33	NM_001772.4	c.205A>G	p.Arg69Gly	missense_variant	2/7	ENST00000262262.5
LOC107985327	XR_007067309.1	n.232-30725T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD33	ENST00000262262.5	c.205A>G	p.Arg69Gly	missense_variant	2/7	1	NM_001772.4	P2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62996 AN: 151928 Hom.: 13695 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.349 AC: 87652 AN: 251434 Hom.: 17236 AF XY: 0.351 AC XY: 47678 AN XY: 135892

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.0806

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.380

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.398 AC: 581802 AN: 1461816 Hom.: 120883 Cov.: 46 AF XY: 0.395 AC XY: 287313 AN XY: 727212

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.0606

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.415 AC: 63034 AN: 152046 Hom.: 13708 Cov.: 31 AF XY: 0.405 AC XY: 30132 AN XY: 74326

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.402

Alfa AF: 0.396 Hom.: 6282

Bravo AF: 0.416

TwinsUK AF: 0.439 AC: 1627

ALSPAC AF: 0.414 AC: 1596

ESP6500AA AF: 0.502 AC: 2210

ESP6500EA AF: 0.430 AC: 3698

ExAC AF: 0.358 AC: 43419

Asia WGS AF: 0.195 AC: 678 AN: 3478

EpiCase AF: 0.427

EpiControl AF: 0.436

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 22, 2019

This variant is associated with the following publications: (PMID: 30917570) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.043
Dann	Benign	0.27
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.0025	T;T
MetaRNN	Benign	0.00015	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.037
Sift	Benign	0.33	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0010	.;B
Vest4		0.070
MPC		0.082
ClinPred		0.018	T
GERP RS		-7.0
Varity_R		0.48
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs2455069; hg19: chr19-51728641; COSMIC: COSV51800308; COSMIC: COSV51800308;