chr20-3691476-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_023068.4(SIGLEC1):​c.4455C>T​(p.Asp1485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,613,472 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0034 ( 21 hom. )

Consequence

SIGLEC1
NM_023068.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.831
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 20-3691476-G-A is Benign according to our data. Variant chr20-3691476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652178.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.831 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.4455C>T p.Asp1485= synonymous_variant 18/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4455C>T p.Asp1485= synonymous_variant 17/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4455C>T p.Asp1485= synonymous_variant 18/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4455C>T p.Asp1485= synonymous_variant 17/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.897C>T p.Asp299= synonymous_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.00269
AC:
410
AN:
152266
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.0331
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00334
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00355
AC:
891
AN:
250664
Hom.:
8
AF XY:
0.00381
AC XY:
517
AN XY:
135696
show subpopulations
Gnomad AFR exome
AF:
0.000370
Gnomad AMR exome
AF:
0.000636
Gnomad ASJ exome
AF:
0.0345
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00297
Gnomad FIN exome
AF:
0.00102
Gnomad NFE exome
AF:
0.00335
Gnomad OTH exome
AF:
0.00392
GnomAD4 exome
AF:
0.00343
AC:
5005
AN:
1461088
Hom.:
21
Cov.:
33
AF XY:
0.00340
AC XY:
2471
AN XY:
726846
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.000872
Gnomad4 ASJ exome
AF:
0.0320
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00263
Gnomad4 FIN exome
AF:
0.00121
Gnomad4 NFE exome
AF:
0.00315
Gnomad4 OTH exome
AF:
0.00459
GnomAD4 genome
AF:
0.00268
AC:
408
AN:
152384
Hom.:
3
Cov.:
33
AF XY:
0.00239
AC XY:
178
AN XY:
74522
show subpopulations
Gnomad4 AFR
AF:
0.000577
Gnomad4 AMR
AF:
0.00104
Gnomad4 ASJ
AF:
0.0331
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00334
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00525
Hom.:
4
Bravo
AF:
0.00267
EpiCase
AF:
0.00267
EpiControl
AF:
0.00391

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023SIGLEC1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
3.2
DANN
Benign
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35702208; hg19: chr20-3672123; API