rs2455069

Variant names:

• chr19-51225385-A-G
• rs2455069
• NM_001772.4:c.205A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-51225385-A-G
• chr19-51225385-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.05
• Publications: 70 publications found

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]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1225488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001772.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	NM_001772.4	MANE Select	c.205A>G	p.Arg69Gly	missense	Exon 2 of 7	NP_001763.3
	CD33	NM_001177608.2		c.205A>G	p.Arg69Gly	missense	Exon 2 of 7	NP_001171079.1
	CD33	NM_001082618.2		c.37+230A>G		intron	N/A	NP_001076087.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000262262.5	TSL:1 MANE Select	c.205A>G	p.Arg69Gly	missense	Exon 2 of 7	ENSP00000262262.3
	CD33	ENST00000391796.7	TSL:1	c.205A>G	p.Arg69Gly	missense	Exon 2 of 7	ENSP00000375673.2
	CD33	ENST00000421133.6	TSL:1	c.37+230A>G		intron	N/A	ENSP00000410126.1

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

GnomAD2 exomes AF: 0.349 AC: 87652 AN: 251434 AF XY: 0.351

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 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

African (AFR) AF: 0.500 AC: 16732 AN: 33478

American (AMR) AF: 0.230 AC: 10283 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10205 AN: 26134

East Asian (EAS) AF: 0.0606 AC: 2404 AN: 39700

South Asian (SAS) AF: 0.256 AC: 22076 AN: 86256

European-Finnish (FIN) AF: 0.385 AC: 20567 AN: 53418

Middle Eastern (MID) AF: 0.408 AC: 2355 AN: 5768

European-Non Finnish (NFE) AF: 0.426 AC: 473849 AN: 1111942

Other (OTH) AF: 0.386 AC: 23331 AN: 60396

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

African (AFR) AF: 0.504 AC: 20880 AN: 41458

American (AMR) AF: 0.305 AC: 4657 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3472

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1140 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3954 AN: 10562

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29131 AN: 67956

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.407 Hom.: 26725

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.21	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.0025	T
MetaRNN	Benign	0.00015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-5.0
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.037
Sift	Benign	0.33	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.070
MPC		0.082
ClinPred		0.018	T
GERP RS		-7.0
PromoterAI		0.16	Neutral
Varity_R		0.48
gMVP		0.17
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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