chr19-51451468-G-T

Variant names:

• chr19-51451468-G-T
• rs10518263
• NM_014442.3:c.*911C>A

Variant summary

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

The NM_014442.3(SIGLEC8):​c.*911C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,182 control chromosomes in the GnomAD database, including 1,997 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 0.15 (1996 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: SIGLEC8 NM_014442.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014442.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC8	NM_014442.3	MANE Select	c.*911C>A		3_prime_UTR	Exon 7 of 7	NP_055257.2
	SIGLEC8	NM_001363548.1		c.*911C>A		3_prime_UTR	Exon 6 of 6	NP_001350477.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC8	ENST00000321424.7	TSL:1 MANE Select	c.*911C>A		3_prime_UTR	Exon 7 of 7	ENSP00000321077.2
	SIGLEC8	ENST00000960611.1		c.*911C>A		3_prime_UTR	Exon 7 of 7	ENSP00000630670.1
	SIGLEC8	ENST00000960610.1		c.*911C>A		3_prime_UTR	Exon 6 of 6	ENSP00000630669.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22922 AN: 152042 Hom.: 1996 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 4 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.151 AC: 22922 AN: 152160 Hom.: 1996 Cov.: 32 AF XY: 0.151 AC XY: 11198 AN XY: 74386

African (AFR) AF: 0.0912 AC: 3785 AN: 41520

American (AMR) AF: 0.129 AC: 1965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.0933 AC: 484 AN: 5186

South Asian (SAS) AF: 0.169 AC: 813 AN: 4824

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10574

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12689 AN: 67986

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.162 Hom.: 2170

Bravo AF: 0.141

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.42
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518263; hg19: chr19-51954722;