rs3826656

Variant names:

• chr19-51223357-G-A
• rs3826656
• XM_011527531.3:c.-51-1299G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011527531.3(CD33):​c.-51-1299G>A 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: CD33 XM_011527531.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 -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

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

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.716

Alfa AF: 0.746 Hom.: 99708

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3826656; hg19: chr19-51726613;