rs1710398

Positions:

• chr19-51223655-A-C

Variant summary

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

The XM_011527531.3(CD33):​c.-51-1001A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,018 control chromosomes in the GnomAD database, including 14,671 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 0.43 (14671 hom., cov: 32)
• Consequence: CD33 XM_011527531.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD33	XM_011527531.3	c.-51-1001A>C		intron_variant			XP_011525833.1
CD33	XM_017027508.2	c.-51-1001A>C		intron_variant			XP_016882997.1
CD33	XM_047439728.1	c.-51-1001A>C		intron_variant			XP_047295684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65000 AN: 151900 Hom.: 14661 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.428 AC: 65044 AN: 152018 Hom.: 14671 Cov.: 32 AF XY: 0.418 AC XY: 31086 AN XY: 74312

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.420

Alfa AF: 0.424 Hom.: 3758

Bravo AF: 0.429

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.66
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1710398; hg19: chr19-51726911;