20-3691244-G-A

Position:

• chr20-3691244-G-A

Variant summary

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

The NM_023068.4(SIGLEC1):​c.4591+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,484,422 control chromosomes in the GnomAD database, including 102,224 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 0.35 (9693 hom., cov: 33)
  • Exomes 𝑓: 0.37 (92531 hom.)
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.4591+96C>T		intron_variant		ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.4591+96C>T		intron_variant			NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.4591+96C>T		intron_variant		1	NM_023068.4	ENSP00000341141	P2
SIGLEC1	ENST00000419548.4	c.1031+96C>T		intron_variant		2		ENSP00000395778
SIGLEC1	ENST00000707083.1	c.4591+96C>T		intron_variant				ENSP00000516734	A2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52756 AN: 152014 Hom.: 9699 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.368 AC: 490508 AN: 1332290 Hom.: 92531 AF XY: 0.370 AC XY: 244418 AN XY: 659940

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.347 AC: 52772 AN: 152132 Hom.: 9693 Cov.: 33 AF XY: 0.356 AC XY: 26450 AN XY: 74384

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.352

Alfa AF: 0.358 Hom.: 2182

Bravo AF: 0.345

Asia WGS AF: 0.404 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.93
DANN	Benign	0.59

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: rs3859664; hg19: chr20-3671891; COSMIC: COSV52463104;