rs114809409

Variant names:

• chr19-51452586-A-C
• rs114809409
• NM_014442.3:c.1293T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-51452586-A-C
• chr19-51452586-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014442.3(SIGLEC8):​c.1293T>G​(p.Pro431Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,571,174 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (31 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (38 hom.)
• Consequence: SIGLEC8 NM_014442.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.43
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 19-51452586-A-C is Benign according to our data. Variant chr19-51452586-A-C is described in ClinVar as Benign. ClinVar VariationId is 769047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.43 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1955/151876) while in subpopulation AFR AF = 0.0443 (1835/41400). AF 95% confidence interval is 0.0426. There are 31 homozygotes in GnomAd4. There are 928 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC8	NM_014442.3	MANE Select	c.1293T>G	p.Pro431Pro	synonymous	Exon 7 of 7	NP_055257.2	Q9NYZ4-1
	SIGLEC8	NM_001363548.1		c.1014T>G	p.Pro338Pro	synonymous	Exon 6 of 6	NP_001350477.1	Q9NYZ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC8	ENST00000321424.7	TSL:1 MANE Select	c.1293T>G	p.Pro431Pro	synonymous	Exon 7 of 7	ENSP00000321077.2	Q9NYZ4-1
	SIGLEC8	ENST00000340550.5	TSL:1	c.1014T>G	p.Pro338Pro	synonymous	Exon 6 of 6	ENSP00000339448.4	Q9NYZ4-2
	SIGLEC8	ENST00000853029.1		c.1260T>G	p.Pro420Pro	synonymous	Exon 7 of 7	ENSP00000523088.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1955 AN: 151758 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00519

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00362 AC: 827 AN: 228606 AF XY: 0.00252

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00222

GnomAD4 exome AF: 0.00125 AC: 1777 AN: 1419298 Hom.: 38 Cov.: 32 AF XY: 0.00105 AC XY: 739 AN XY: 700620

African (AFR) AF: 0.0446 AC: 1424 AN: 31932

American (AMR) AF: 0.00287 AC: 116 AN: 40410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24522

East Asian (EAS) AF: 0.00 AC: 0 AN: 38912

South Asian (SAS) AF: 0.0000488 AC: 4 AN: 81988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52354

Middle Eastern (MID) AF: 0.00199 AC: 11 AN: 5530

European-Non Finnish (NFE) AF: 0.0000544 AC: 59 AN: 1085380

Other (OTH) AF: 0.00280 AC: 163 AN: 58270

GnomAD4 genome AF: 0.0129 AC: 1955 AN: 151876 Hom.: 31 Cov.: 31 AF XY: 0.0125 AC XY: 928 AN XY: 74252

African (AFR) AF: 0.0443 AC: 1835 AN: 41400

American (AMR) AF: 0.00505 AC: 77 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67924

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

Alfa AF: 0.00734 Hom.: 7

Bravo AF: 0.0144

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism

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: rs114809409; hg19: chr19-51955840;