20-3691476-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_023068.4(SIGLEC1):c.4455C>T(p.Asp1485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,613,472 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (21 hom.)
• Consequence: SIGLEC1 NM_023068.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.831

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-3691476-G-A is Benign according to our data. Variant chr20-3691476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.831 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.4455C>T	p.Asp1485=	synonymous_variant	18/22	ENST00000344754.6
SIGLEC1	NM_001367089.1	c.4455C>T	p.Asp1485=	synonymous_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.4455C>T	p.Asp1485=	synonymous_variant	18/22	1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.4455C>T	p.Asp1485=	synonymous_variant	17/20			A2
SIGLEC1	ENST00000419548.4	c.897C>T	p.Asp299=	synonymous_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 410 AN: 152266 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00355 AC: 891 AN: 250664 Hom.: 8 AF XY: 0.00381 AC XY: 517 AN XY: 135696

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.0345

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00297

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00335

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00343 AC: 5005 AN: 1461088 Hom.: 21 Cov.: 33 AF XY: 0.00340 AC XY: 2471 AN XY: 726846

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00263

Gnomad4 FIN exome AF: 0.00121

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.00268 AC: 408 AN: 152384 Hom.: 3 Cov.: 33 AF XY: 0.00239 AC XY: 178 AN XY: 74522

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00104

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00334

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00525 Hom.: 4

Bravo AF: 0.00267

EpiCase AF: 0.00267

EpiControl AF: 0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SIGLEC1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	3.2
Dann	Benign	0.55

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: rs35702208; hg19: chr20-3672123;