dbSNP rs3859664: SIGLEC1:c.4591+96C>T (chr20-3691244-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023068.4(SIGLEC1):c.4591+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,484,422 control chromosomes in the GnomAD database, including 102,224 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 0.35 ( 9693 hom., cov: 33)

Exomes 𝑓: 0.37 ( 92531 hom. )

Consequence

SIGLEC1
NM_023068.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.4591+96C>T		intron_variant	Intron 18 of 21	ENST00000344754.6	NP_075556.1	Q9BZZ2-1
SIGLEC1	NM_001367089.1 link	c.4591+96C>T		intron_variant	Intron 17 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIGLEC1	ENST00000344754.6 link	c.4591+96C>T	intron_variant	Intron 18 of 21	1	NM_023068.4	ENSP00000341141.4	Q9BZZ2-1
SIGLEC1	ENST00000707083.1 link	c.4591+96C>T	intron_variant	Intron 17 of 19			ENSP00000516734.1	Q9BZZ2-3
SIGLEC1	ENST00000419548.4 link	c.1030+96C>T	intron_variant	Intron 4 of 4	2		ENSP00000395778.1	H7C0M6

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52756

AN:

152014

Hom.:

9699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.368

AC:

490508

AN:

1332290

Hom.:

92531

AF XY:

0.370

AC XY:

244418

AN XY:

659940

show subpopulations

African (AFR)

AF:

0.249

AC:

7750

AN:

31070

American (AMR)

AF:

0.557

AC:

23474

AN:

42106

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

8628

AN:

22978

East Asian (EAS)

AF:

0.378

AC:

14577

AN:

38596

South Asian (SAS)

AF:

0.459

AC:

35324

AN:

76928

European-Finnish (FIN)

AF:

0.420

AC:

21041

AN:

50092

Middle Eastern (MID)

AF:

0.367

AC:

1930

AN:

5266

European-Non Finnish (NFE)

AF:

0.354

AC:

357667

AN:

1009456

Other (OTH)

AF:

0.361

AC:

20117

AN:

55798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

16028

32057

48085

64114

80142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.347

AC:

52772

AN:

152132

Hom.:

9693

Cov.:

AF XY:

0.356

AC XY:

26450

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.251

AC:

10404

AN:

41506

American (AMR)

AF:

0.466

AC:

7113

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1280

AN:

3472

East Asian (EAS)

AF:

0.393

AC:

2037

AN:

5182

South Asian (SAS)

AF:

0.469

AC:

2264

AN:

4824

European-Finnish (FIN)

AF:

0.419

AC:

4428

AN:

10562

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.357

AC:

24245

AN:

67988

Other (OTH)

AF:

0.352

AC:

745

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1741

3482

5223

6964

8705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.359

Hom.:

3895

Bravo

AF:

0.345

Asia WGS

AF:

0.404

AC:

1409

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.93

(source)

DANN

Benign

0.59

PhyloP100

-0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3859664

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