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20-3691922-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_023068.4(SIGLEC1):c.4311C>T(p.Ile1437=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,584,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SIGLEC1
NM_023068.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.568
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-3691922-G-A is Benign according to our data. Variant chr20-3691922-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652180.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.568 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SIGLEC1NM_023068.4 linkuse as main transcriptc.4311C>T p.Ile1437= synonymous_variant 17/22 ENST00000344754.6
SIGLEC1NM_001367089.1 linkuse as main transcriptc.4311C>T p.Ile1437= synonymous_variant 16/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SIGLEC1ENST00000344754.6 linkuse as main transcriptc.4311C>T p.Ile1437= synonymous_variant 17/221 NM_023068.4 P2Q9BZZ2-1
SIGLEC1ENST00000707083.1 linkuse as main transcriptc.4311C>T p.Ile1437= synonymous_variant 16/20 A2
SIGLEC1ENST00000419548.4 linkuse as main transcriptc.753C>T p.Ile251= synonymous_variant 3/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000125
AC:
19
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000151
AC:
36
AN:
239142
Hom.:
0
AF XY:
0.000201
AC XY:
26
AN XY:
129158
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.0000591
Gnomad ASJ exome
AF:
0.000670
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000355
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000197
Gnomad OTH exome
AF:
0.000681
GnomAD4 exome
AF:
0.000182
AC:
260
AN:
1432296
Hom.:
0
Cov.:
32
AF XY:
0.000191
AC XY:
135
AN XY:
706838
show subpopulations
Gnomad4 AFR exome
AF:
0.000121
Gnomad4 AMR exome
AF:
0.000114
Gnomad4 ASJ exome
AF:
0.000761
Gnomad4 EAS exome
AF:
0.0000512
Gnomad4 SAS exome
AF:
0.0000359
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000183
Gnomad4 OTH exome
AF:
0.000271
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000125
AC:
19
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000259
Hom.:
0
Bravo
AF:
0.000159

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 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.38
Dann
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs754759740; hg19: chr20-3672569; COSMIC: COSV52458517; API