Genetic Variant SIGLEC5:c.1464+4642C>G (chr19-51621390-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003830.4(SIGLEC5):c.1464+4642C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,090 control chromosomes in the GnomAD database, including 7,707 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 0.30 ( 7707 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SIGLEC5
NM_003830.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.282

Publications

4 publications found

Variant links:

Genes affected

SIGLEC5 (HGNC:10874): (sialic acid binding Ig like lectin 5) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. The encoded protein is a member of the CD33-related subset of Siglecs and inhibits the activation of several cell types including monocytes, macrophages and neutrophils. Binding of group B Streptococcus (GBS) to the encoded protein plays a role in GBS immune evasion. [provided by RefSeq, Feb 2012]

SIGLEC5 links:

RPL9P33 (HGNC:36273): (ribosomal protein L9 pseudogene 33)

RPL9P33 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003830.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIGLEC5	NM_003830.4	MANE Select	c.1464+4642C>G	intron	N/A	NP_003821.1
SIGLEC5	NM_001384708.1		c.1382+5759C>G	intron	N/A	NP_001371637.1
SIGLEC5	NM_001384709.1		c.1179+4642C>G	intron	N/A	NP_001371638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SIGLEC5	ENST00000683636.1	MANE Select	c.1464+4642C>G	intron	N/A	ENSP00000507738.1
RPL9P33	ENST00000484311.1	TSL:6	n.255G>C	non_coding_transcript_exon	Exon 1 of 1
SIGLEC5	ENST00000850616.1		c.1179+4642C>G	intron	N/A	ENSP00000520903.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45403

AN:

151972

Hom.:

7690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.269

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.299

AC:

45473

AN:

152090

Hom.:

7707

Cov.:

AF XY:

0.296

AC XY:

22043

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.461

AC:

19103

AN:

41456

American (AMR)

AF:

0.269

AC:

4109

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

629

AN:

3472

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5180

South Asian (SAS)

AF:

0.216

AC:

1040

AN:

4820

European-Finnish (FIN)

AF:

0.259

AC:

2736

AN:

10564

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16277

AN:

67996

Other (OTH)

AF:

0.266

AC:

561

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.282

Hom.:

834

Bravo

AF:

0.305

Asia WGS

AF:

0.207

AC:

721

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.70

PhyloP100

-0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over