chr19-51623881-C-T

Position:

• chr19-51623881-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003830.4(SIGLEC5):​c.1464+2151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,234 control chromosomes in the GnomAD database, including 58,784 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 0.88 (58784 hom., cov: 31)
• Consequence: SIGLEC5 NM_003830.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC5	NM_003830.4	c.1464+2151G>A		intron_variant		ENST00000683636.1	NP_003821.1
SIGLEC5	NM_001384708.1	c.1382+3268G>A		intron_variant			NP_001371637.1
SIGLEC5	NM_001384709.1	c.1179+2151G>A		intron_variant			NP_001371638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC5	ENST00000683636.1	c.1464+2151G>A		intron_variant			NM_003830.4	ENSP00000507738	P1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133440 AN: 152116 Hom.: 58722 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.850

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133561 AN: 152234 Hom.: 58784 Cov.: 31 AF XY: 0.878 AC XY: 65355 AN XY: 74424

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.786

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.852

Alfa AF: 0.839 Hom.: 107660

Bravo AF: 0.882

Asia WGS AF: 0.869 AC: 3022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.82
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs4802831; hg19: chr19-52127134;