rs6076542

Positions:

• chr20-3705350-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_023068.4(SIGLEC1):​c.706+394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,318 control chromosomes in the GnomAD database, including 83 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 0.027 (83 hom., cov: 34)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0268 (4080/152318) while in subpopulation NFE AF= 0.0383 (2605/68026). AF 95% confidence interval is 0.0371. There are 83 homozygotes in gnomad4. There are 1973 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 83 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.706+394A>G		intron_variant		ENST00000344754.6
SIGLEC1	NM_001367089.1	c.706+394A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.706+394A>G		intron_variant		1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.706+394A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4075 AN: 152200 Hom.: 83 Cov.: 34

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0268 AC: 4080 AN: 152318 Hom.: 83 Cov.: 34 AF XY: 0.0265 AC XY: 1973 AN XY: 74474

Gnomad4 AFR AF: 0.00748

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00662

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0337 Hom.: 23

Bravo AF: 0.0244

Asia WGS AF: 0.00346 AC: 12 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	3.3
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6076542; hg19: chr20-3685997;