rs3826656

Variant names:

• chr19-51223357-G-A
• rs3826656
• ENST00000716537.1:n.244-28697C>T

Variant summary

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

The ENST00000716537.1(ENSG00000268595):​n.244-28697C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,160 control chromosomes in the GnomAD database, including 43,683 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 0.75 (43683 hom., cov: 32)
• Consequence: ENSG00000268595 ENST00000716537.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 65 publications found

Genes affected

ENSG00000268595 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD33	XM_011527531.3	c.-51-1299G>A		intron_variant	Intron 5 of 12		XP_011525833.1
CD33	XM_017027508.2	c.-51-1299G>A		intron_variant	Intron 5 of 12		XP_016882997.1
CD33	XM_047439728.1	c.-51-1299G>A		intron_variant	Intron 4 of 11		XP_047295684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268595	ENST00000716537.1	n.244-28697C>T		intron_variant	Intron 2 of 4
ENSG00000268595	ENST00000716538.1	n.244-28697C>T		intron_variant	Intron 2 of 4
ENSG00000268595	ENST00000716539.1	n.246-28697C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113903 AN: 152042 Hom.: 43637 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.749 AC: 114003 AN: 152160 Hom.: 43683 Cov.: 32 AF XY: 0.741 AC XY: 55100 AN XY: 74382

African (AFR) AF: 0.817 AC: 33938 AN: 41524

American (AMR) AF: 0.766 AC: 11717 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1535 AN: 5168

South Asian (SAS) AF: 0.452 AC: 2181 AN: 4824

European-Finnish (FIN) AF: 0.748 AC: 7911 AN: 10576

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.768 AC: 52227 AN: 67992

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.750 Hom.: 159293

Bravo AF: 0.758

Asia WGS AF: 0.441 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.42
PhyloP100		-0.078

Splicing

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

Other links and lift over

dbSNP: rs3826656; hg19: chr19-51726613;