rs4815596

Positions:

• chr20-3691153-G-A
• chr20-3691153-G-T

Variant summary

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

The NM_023068.4(SIGLEC1):​c.4591+187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,084 control chromosomes in the GnomAD database, including 3,205 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 0.19 (3205 hom., cov: 31)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]

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 = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.4591+187C>T		intron_variant		ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.4591+187C>T		intron_variant			NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.4591+187C>T		intron_variant		1	NM_023068.4	ENSP00000341141	P2
SIGLEC1	ENST00000419548.4	c.1031+187C>T		intron_variant		2		ENSP00000395778
SIGLEC1	ENST00000707083.1	c.4591+187C>T		intron_variant				ENSP00000516734	A2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29402 AN: 151966 Hom.: 3196 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29433 AN: 152084 Hom.: 3205 Cov.: 31 AF XY: 0.194 AC XY: 14453 AN XY: 74350

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.179

Alfa AF: 0.156 Hom.: 1237

Bravo AF: 0.193

Asia WGS AF: 0.224 AC: 779 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	0.96
DANN	Benign	0.46

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: rs4815596; hg19: chr20-3671800;