chr19-49975821-C-T

Variant names:

• chr19-49975821-C-T
• rs12984584
• ENST00000602139.6:c.*2313C>T

Variant summary

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

The ENST00000602139.6(SIGLEC16):​c.*2313C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,114 control chromosomes in the GnomAD database, including 2,674 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 (2674 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SIGLEC16 ENST00000602139.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 8 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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 rank	MANE	Protein	UniProt
SIGLEC16	NM_001348364.2	c.*2334C>T		downstream_gene_variant			NP_001335293.2
SIGLEC16	NR_145574.2	n.*7C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC16	ENST00000602139.6	c.*2313C>T		downstream_gene_variant		5		ENSP00000502223.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27456 AN: 151966 Hom.: 2669 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.133 AC: 4 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 4 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 4 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.181 AC: 27477 AN: 152084 Hom.: 2674 Cov.: 32 AF XY: 0.179 AC XY: 13302 AN XY: 74348

African (AFR) AF: 0.161 AC: 6666 AN: 41488

American (AMR) AF: 0.149 AC: 2276 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3464

East Asian (EAS) AF: 0.326 AC: 1681 AN: 5158

South Asian (SAS) AF: 0.141 AC: 677 AN: 4812

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10590

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13277 AN: 67994

Other (OTH) AF: 0.188 AC: 396 AN: 2108

Alfa AF: 0.194 Hom.: 485

Bravo AF: 0.183

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs12984584; hg19: chr19-50479078;