chr19-51223655-A-C

Variant names:

• chr19-51223655-A-C
• rs1710398
• ENST00000716537.1:n.244-28995T>G

Variant summary

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

The ENST00000716537.1(ENSG00000268595):​n.244-28995T>G 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: ENSG00000268595 ENST00000716537.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 12 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=-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 rank	MANE	Protein	UniProt
CD33	XM_011527531.3	c.-51-1001A>C		intron_variant	Intron 5 of 12		XP_011525833.1
CD33	XM_017027508.2	c.-51-1001A>C		intron_variant	Intron 5 of 12		XP_016882997.1
CD33	XM_047439728.1	c.-51-1001A>C		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.244-28995T>G		intron_variant	Intron 2 of 4
ENSG00000268595	ENST00000716538.1	n.244-28995T>G		intron_variant	Intron 2 of 4
ENSG00000268595	ENST00000716539.1	n.246-28995T>G		intron_variant	Intron 2 of 3

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

African (AFR) AF: 0.544 AC: 22542 AN: 41428

American (AMR) AF: 0.307 AC: 4697 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3472

East Asian (EAS) AF: 0.0847 AC: 439 AN: 5182

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4816

European-Finnish (FIN) AF: 0.383 AC: 4041 AN: 10544

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29211 AN: 67982

Other (OTH) AF: 0.420 AC: 887 AN: 2110

Alfa AF: 0.417 Hom.: 8651

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
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs1710398; hg19: chr19-51726911;