ENST00000945453.1:c.-38C>A

Variant names:

• chr19-51224706-C-A
• rs3865444
• ENST00000945453.1:c.-38C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000945453.1(CD33):​c.-38C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,044 control chromosomes in the GnomAD database, including 6,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6038 hom., cov: 31)
• Consequence: CD33 ENST00000945453.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 337 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000945453.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000945453.1		c.-38C>A		5_prime_UTR	Exon 2 of 9	ENSP00000615512.1
	ENSG00000268595	ENST00000716537.1		n.244-30046G>T		intron	N/A
	ENSG00000268595	ENST00000716538.1		n.244-30046G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38556 AN: 151926 Hom.: 6026 Cov.: 31

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38576 AN: 152044 Hom.: 6038 Cov.: 31 AF XY: 0.258 AC XY: 19175 AN XY: 74316

African (AFR) AF: 0.0868 AC: 3598 AN: 41472

American (AMR) AF: 0.428 AC: 6538 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3470

East Asian (EAS) AF: 0.188 AC: 972 AN: 5180

South Asian (SAS) AF: 0.156 AC: 754 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3788 AN: 10548

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21445 AN: 67956

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.297 Hom.: 33763

Bravo AF: 0.255

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.48
PhyloP100		-1.6
PromoterAI		0.040	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3865444;

hg19: chr19-51727962;