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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.*1125C>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000344754.6	NP_075556.1	Q9BZZ2-1
SIGLEC1	NM_001367089.1 link	c.*1076C>A		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.*1125C>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_023068.4	ENSP00000341141.4		Q9BZZ2-1
SIGLEC1	ENST00000419548.4 link	c.*2471C>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000395778.1		H7C0M6

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over