rs1803254

Variant names:

• chr19-51239889-G-C
• rs1803254
• NM_001772.4:c.*201G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-51239889-G-C
• chr19-51239889-G-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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.152
• Publications: 21 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 (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.

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.*201G>C		3_prime_UTR	Exon 7 of 7	NP_001763.3	Q546G0
	CD33	NM_001082618.2		c.*201G>C		3_prime_UTR	Exon 6 of 6	NP_001076087.1	P20138-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000262262.5	TSL:1 MANE Select	c.*201G>C		3_prime_UTR	Exon 7 of 7	ENSP00000262262.3	P20138-1
	CD33	ENST00000421133.6	TSL:1	c.*201G>C		3_prime_UTR	Exon 6 of 6	ENSP00000410126.1	P20138-3
	CD33	ENST00000945453.1		c.*201G>C		3_prime_UTR	Exon 9 of 9	ENSP00000615512.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24626 AN: 152010 Hom.: 3101 Cov.: 32

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.: 4 AF XY: 0.102 AC XY: 14816 AN XY: 145642

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

GnomAD4 genome AF: 0.162 AC: 24687 AN: 152130 Hom.: 3114 Cov.: 32 AF XY: 0.164 AC XY: 12185 AN XY: 74382

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: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4821 AN: 67990

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.0495 Hom.: 48

Bravo AF: 0.190

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		0.15
Mutation Taster		=100/0	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: rs1803254; hg19: chr19-51743144; COSMIC: COSV51803488; COSMIC: COSV51803488;