Genetic Variant 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023068.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	NM_023068.4	MANE Select	c.4591+96C>T		intron	N/A	NP_075556.1
	SIGLEC1	NM_001367089.1		c.4591+96C>T		intron	N/A	NP_001354018.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIGLEC1	ENST00000344754.6	TSL:1 MANE Select	c.4591+96C>T	intron	N/A	ENSP00000341141.4
SIGLEC1	ENST00000707083.1		c.4591+96C>T	intron	N/A	ENSP00000516734.1
SIGLEC1	ENST00000419548.4	TSL:2	c.1030+96C>T	intron	N/A	ENSP00000395778.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

11404

22808

34212

45616

57020

<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:

0.347

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.359

Hom.:

3895

Bravo

AF:

0.345

Asia WGS

AF:

0.404

AC:

1409

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over