rs625372

chr20-3704082-T-C

Variant summary

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

The NM_023068.4(SIGLEC1):c.716A>G(p.Lys239Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,611,512 control chromosomes in the GnomAD database, including 332,206 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.63 (30205 hom., cov: 31)
  • Exomes 𝑓: 0.64 (302001 hom.)
• Consequence: SIGLEC1 NM_023068.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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 (MetaRNN=2.3265331E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.716A>G	p.Lys239Arg	missense_variant	5/22	ENST00000344754.6
SIGLEC1	NM_001367089.1	c.716A>G	p.Lys239Arg	missense_variant	4/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.716A>G	p.Lys239Arg	missense_variant	5/22	1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.716A>G	p.Lys239Arg	missense_variant	4/20			A2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95440 AN: 151654 Hom.: 30169 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.623

GnomAD3 exomes AF: 0.644 AC: 160335 AN: 248878 Hom.: 52041 AF XY: 0.647 AC XY: 87094 AN XY: 134716

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.614

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.642 AC: 936935 AN: 1459740 Hom.: 302001 Cov.: 50 AF XY: 0.642 AC XY: 466219 AN XY: 725982

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.638

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.629 AC: 95517 AN: 151772 Hom.: 30205 Cov.: 31 AF XY: 0.637 AC XY: 47234 AN XY: 74198

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.618

Alfa AF: 0.642 Hom.: 63416

Bravo AF: 0.613

TwinsUK AF: 0.639 AC: 2369

ALSPAC AF: 0.641 AC: 2470

ESP6500AA AF: 0.561 AC: 2472

ESP6500EA AF: 0.644 AC: 5542

ExAC AF: 0.644 AC: 78231

Asia WGS AF: 0.629 AC: 2190 AN: 3478

EpiCase AF: 0.643

EpiControl AF: 0.645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.4
Dann	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.48	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.061
Sift	Benign	0.21	T
Sift4G	Benign	0.59	T
Polyphen		0.034	B
Vest4		0.029
MPC		0.12
ClinPred		0.0051	T
GERP RS		-3.2
Varity_R		0.080
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs625372; hg19: chr20-3684729; COSMIC: COSV52466532;