dbSNP rs6076542: SIGLEC1:c.706+394A>G (chr20-3705350-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

1 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=-0.91).

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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 83 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.706+394A>G		intron_variant	Intron 4 of 21	ENST00000344754.6	NP_075556.1	Q9BZZ2-1
SIGLEC1	NM_001367089.1 link	c.706+394A>G		intron_variant	Intron 3 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 link	c.706+394A>G		intron_variant	Intron 4 of 21	1	NM_023068.4	ENSP00000341141.4		Q9BZZ2-1
SIGLEC1	ENST00000707083.1 link	c.706+394A>G		intron_variant	Intron 3 of 19			ENSP00000516734.1		Q9BZZ2-3

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4075

AN:

152200

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0265

AC XY:

1973

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00748

AC:

311

AN:

41570

American (AMR)

AF:

0.0197

AC:

302

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00662

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0539

AC:

572

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0383

AC:

2605

AN:

68026

Other (OTH)

AF:

0.0237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

208

416

623

831

1039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0337

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.00346

AC:

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

(source)

DANN

Benign

0.69

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over