rs39711

Positions:

• chr19-51451604-T-C

Variant summary

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

The NM_014442.3(SIGLEC8):​c.*775A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,080 control chromosomes in the GnomAD database, including 10,449 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 0.34 (10449 hom., cov: 32)
  • Exomes 𝑓: 0.50 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGLEC8 NM_014442.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC8	NM_014442.3	c.*775A>G		3_prime_UTR_variant	7/7	ENST00000321424.7
SIGLEC8	NM_001363548.1	c.*775A>G		3_prime_UTR_variant	6/6
SIGLEC8	XM_011526734.3	c.*775A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC8	ENST00000321424.7	c.*775A>G		3_prime_UTR_variant	7/7	1	NM_014442.3	P1
SIGLEC8	ENST00000430817.5	c.*42-509A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52347 AN: 151962 Hom.: 10419 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.319

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.500 AC: 14 AN: 28 Hom.: 3 Cov.: 0 AF XY: 0.611 AC XY: 11 AN XY: 18

Gnomad4 AFR exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.556

GnomAD4 genome AF: 0.345 AC: 52425 AN: 152080 Hom.: 10449 Cov.: 32 AF XY: 0.347 AC XY: 25810 AN XY: 74342

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.322

Alfa AF: 0.263 Hom.: 11386

Bravo AF: 0.345

Asia WGS AF: 0.445 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs39711; hg19: chr19-51954858;