Genetic Variant NM_023068.4:c.*1125C>A (chr20-3687435-G-T) – 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.*1125C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,084 control chromosomes in the GnomAD database, including 17,289 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 0.48 ( 17282 hom., cov: 32)

Exomes 𝑓: 0.48 ( 7 hom. )

Consequence

SIGLEC1
NM_023068.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.273

Publications

14 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).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	NM_023068.4	MANE Select	c.*1125C>A		3_prime_UTR	Exon 22 of 22	NP_075556.1	Q9BZZ2-1
	SIGLEC1	NM_001367089.1		c.*1076C>A		3_prime_UTR	Exon 20 of 20	NP_001354018.1	Q9BZZ2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIGLEC1	ENST00000344754.6	TSL:1 MANE Select	c.*1125C>A	3_prime_UTR	Exon 22 of 22	ENSP00000341141.4	Q9BZZ2-1
SIGLEC1	ENST00000869141.1		c.*1125C>A	3_prime_UTR	Exon 22 of 22	ENSP00000539200.1
SIGLEC1	ENST00000869142.1		c.*1125C>A	3_prime_UTR	Exon 22 of 22	ENSP00000539201.1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72291

AN:

151908

Hom.:

17276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.483

AC:

AN:

Hom.:

Cov.:

AF XY:

0.531

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.476

AC:

72334

AN:

152024

Hom.:

17282

Cov.:

AF XY:

0.481

AC XY:

35765

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.455

AC:

18858

AN:

41470

American (AMR)

AF:

0.518

AC:

7915

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1647

AN:

3470

East Asian (EAS)

AF:

0.388

AC:

1996

AN:

5150

South Asian (SAS)

AF:

0.554

AC:

2667

AN:

4818

European-Finnish (FIN)

AF:

0.530

AC:

5593

AN:

10560

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.475

AC:

32295

AN:

67958

Other (OTH)

AF:

0.487

AC:

1028

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1953

3907

5860

7814

9767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.484

Hom.:

34269

Bravo

AF:

0.475

Asia WGS

AF:

0.413

AC:

1437

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.62

(source)

DANN

Benign

0.36

PhyloP100

-0.27

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