20-3688588-GT-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_023068.4(SIGLEC1):c.5101del(p.Thr1701ProfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,603,222 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: SIGLEC1 NM_023068.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

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 -8 ACMG points.

• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1737 codons.
• BP6: Variant 20-3688588-GT-G is Benign according to our data. Variant chr20-3688588-GT-G is described in ClinVar as [Benign]. Clinvar id is 730631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00117 (1703/1450928) while in subpopulation SAS AF= 0.0163 (1364/83924). AF 95% confidence interval is 0.0155. There are 24 homozygotes in gnomad4_exome. There are 1176 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.5101del	p.Thr1701ProfsTer26	frameshift_variant	22/22	ENST00000344754.6
SIGLEC1	NM_001367089.1	c.5028del	p.Arg1676SerfsTer32	frameshift_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.5101del	p.Thr1701ProfsTer26	frameshift_variant	22/22	1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.5028del	p.Arg1676SerfsTer?	frameshift_variant	20/20			A2
SIGLEC1	ENST00000419548.4	c.*1317del		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00211 AC: 489 AN: 231930 Hom.: 6 AF XY: 0.00286 AC XY: 358 AN XY: 125194

Gnomad AFR exome AF: 0.0000703

Gnomad AMR exome AF: 0.000152

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00117 AC: 1703 AN: 1450928 Hom.: 24 Cov.: 30 AF XY: 0.00163 AC XY: 1176 AN XY: 720550

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000234

Gnomad4 OTH exome AF: 0.000950

GnomAD4 genome AF: 0.000795 AC: 121 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.00114 AC XY: 85 AN XY: 74472

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000545 Hom.: 0

Bravo AF: 0.000317

Asia WGS AF: 0.00895 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs375405123; hg19: chr20-3669235;