Genetic Variant SIGLEC1:p.Asn350Asn (chr20-3703375-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_023068.4(SIGLEC1):c.1050T>C(p.Asn350Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,612,216 control chromosomes in the GnomAD database, including 332,927 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 0.63 ( 30420 hom., cov: 32)

Exomes 𝑓: 0.64 ( 302507 hom. )

Consequence

SIGLEC1
NM_023068.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.09

Publications

22 publications found

Variant links:

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]

SIGLEC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-3.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.1050T>C	p.Asn350Asn	synonymous_variant	Exon 6 of 22	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1 link	c.1050T>C	p.Asn350Asn	synonymous_variant	Exon 5 of 20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 link	c.1050T>C	p.Asn350Asn	synonymous_variant	Exon 6 of 22	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1 link	c.1050T>C	p.Asn350Asn	synonymous_variant	Exon 5 of 20			ENSP00000516734.1

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95861

AN:

151962

Hom.:

30383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.672

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.622

GnomAD2 exomes

AF:

0.645

AC:

161277

AN:

249904

AF XY:

0.647

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.655

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.642

AC:

937973

AN:

1460136

Hom.:

302507

Cov.:

AF XY:

0.643

AC XY:

466721

AN XY:

726224

show subpopulations

African (AFR)

AF:

0.578

AC:

19343

AN:

33474

American (AMR)

AF:

0.600

AC:

26749

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

16586

AN:

26006

East Asian (EAS)

AF:

0.683

AC:

27114

AN:

39682

South Asian (SAS)

AF:

0.612

AC:

52610

AN:

85974

European-Finnish (FIN)

AF:

0.741

AC:

39554

AN:

53368

Middle Eastern (MID)

AF:

0.609

AC:

3506

AN:

5758

European-Non Finnish (NFE)

AF:

0.642

AC:

713611

AN:

1110960

Other (OTH)

AF:

0.645

AC:

38900

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

18874

37749

56623

75498

94372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18772

37544

56316

75088

93860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.631

AC:

95940

AN:

152080

Hom.:

30420

Cov.:

AF XY:

0.638

AC XY:

47462

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.576

AC:

23886

AN:

41448

American (AMR)

AF:

0.627

AC:

9584

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2172

AN:

3468

East Asian (EAS)

AF:

0.673

AC:

3477

AN:

5170

South Asian (SAS)

AF:

0.618

AC:

2979

AN:

4818

European-Finnish (FIN)

AF:

0.748

AC:

7938

AN:

10606

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44093

AN:

67958

Other (OTH)

AF:

0.618

AC:

1307

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1849

3699

5548

7398

9247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.639

Hom.:

138156

Bravo

AF:

0.615

Asia WGS

AF:

0.631

AC:

2196

AN:

3478

EpiCase

AF:

0.643

EpiControl

AF:

0.646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.10

(source)

DANN

Benign

0.26

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over