rs36489

Positions:

• chr19-51450840-A-G
• chr19-51450840-A-T

Variant summary

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

The 19-51450840-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,152 control chromosomes in the GnomAD database, including 3,050 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 0.19 (3050 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SIGLEC8 ENST00000430817.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

Genes affected

SIGLEC8 (HGNC:10877): (sialic acid binding Ig like lectin 8) Sialic acid-binding immunoglobulin (Ig)-like lectins, or SIGLECs (e.g., CD33 (MIM 159590)), are a family of type 1 transmembrane proteins each having a unique expression pattern, mostly in hemopoietic cells. SIGLEC8 is a member of the CD33-like subgroup of SIGLECs, which are localized to 19q13.3-q13.4 and have 2 conserved cytoplasmic tyrosine-based motifs: an immunoreceptor tyrosine-based inhibitory motif, or ITIM (see MIM 604964), and a motif homologous to one identified in signaling lymphocyte activation molecule (SLAM; MIM 603492) that mediates an association with SLAM-associated protein (SAP; MIM 300490) (summarized by Foussias et al., 2000 [PubMed 11095983]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC8	ENST00000430817.5			downstream_gene_variant		2		ENSP00000389142

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28398 AN: 152032 Hom.: 3051 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.187 AC: 28395 AN: 152150 Hom.: 3050 Cov.: 32 AF XY: 0.189 AC XY: 14029 AN XY: 74380

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.174

Alfa AF: 0.185 Hom.: 4814

Bravo AF: 0.180

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36489; hg19: chr19-51954094;