rs12462972

Positions:

• chr19-49971760-G-A

Variant summary

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

The NM_001348364.2(SIGLEC16):​c.1015+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,607,248 control chromosomes in the GnomAD database, including 29,475 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 0.18 (3009 hom., cov: 30)
  • Exomes 𝑓: 0.19 (26466 hom.)
• Consequence: SIGLEC16 NM_001348364.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

SIGLEC16 (HGNC:24851): (sialic acid binding Ig like lectin 16) Predicted to enable sialic acid binding activity. Involved in positive regulation of defense response to bacterium and positive regulation of interleukin-6 production. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SIGLEC16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC16	NM_001348364.2	c.1015+46G>A		intron_variant			NP_001335293.2
SIGLEC16	NR_145574.2	n.1055+46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC16	ENST00000602139.6	c.1017+46G>A		intron_variant		5		ENSP00000502223.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27333 AN: 151484 Hom.: 3005 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.185 AC: 46388 AN: 250160 Hom.: 4583 AF XY: 0.186 AC XY: 25099 AN XY: 135208

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.320

Gnomad SAS exome AF: 0.149

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.185 AC: 269671 AN: 1455646 Hom.: 26466 Cov.: 40 AF XY: 0.185 AC XY: 134200 AN XY: 724258

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.180 AC: 27353 AN: 151602 Hom.: 3009 Cov.: 30 AF XY: 0.179 AC XY: 13229 AN XY: 74076

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.191

Alfa AF: 0.204 Hom.: 669

Bravo AF: 0.183

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12462972; hg19: chr19-50475017; COSMIC: COSV57465026;