Genetic Variant SIGLEC1:c.*1382T>C (chr20-3687178-A-G) – 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.*1382T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,182 control chromosomes in the GnomAD database, including 2,937 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 0.19 ( 2936 hom., cov: 33)

Exomes 𝑓: 0.20 ( 1 hom. )

Consequence

SIGLEC1
NM_023068.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.531

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.*1382T>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1 link	c.*1333T>C		3_prime_UTR_variant	Exon 20 of 20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 link	c.*1382T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000419548.4 link	c.*2728T>C		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000395778.1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29352

AN:

152034

Hom.:

2929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.190

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.136

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.193

AC:

29387

AN:

152152

Hom.:

2936

Cov.:

AF XY:

0.192

AC XY:

14298

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.190

AC:

7883

AN:

41506

American (AMR)

AF:

0.153

AC:

2336

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3470

East Asian (EAS)

AF:

0.372

AC:

1920

AN:

5166

South Asian (SAS)

AF:

0.127

AC:

613

AN:

4826

European-Finnish (FIN)

AF:

0.206

AC:

2180

AN:

10596

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13052

AN:

67994

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1232

2463

3695

4926

6158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.188

Hom.:

2486

Bravo

AF:

0.189

Asia WGS

AF:

0.231

AC:

804

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.7

(source)

DANN

Benign

0.79

PhyloP100

0.53

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over