11-124668099-T-C

Position:

• chr11-124668099-T-C

Variant summary

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

The ENST00000263593.8(SIAE):​c.229+1261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,202 control chromosomes in the GnomAD database, including 62,519 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 0.90 (62519 hom., cov: 31)
• Consequence: SIAE ENST00000263593.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

Genes affected

SIAE (HGNC:18187): (sialic acid acetylesterase) This gene encodes an enzyme which removes 9-O-acetylation modifications from sialic acids. Mutations in this gene are associated with susceptibility to autoimmune disease 6. Multiple transcript variants encoding different isoforms, found either in the cytosol or in the lysosome, have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIAE	NM_170601.5	c.229+1261A>G		intron_variant		ENST00000263593.8	NP_733746.1
SIAE	NM_001199922.2	c.124+1261A>G		intron_variant			NP_001186851.1
SIAE	XM_047427133.1	c.229+1261A>G		intron_variant			XP_047283089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAE	ENST00000263593.8	c.229+1261A>G		intron_variant		1	NM_170601.5	ENSP00000263593	P2

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137487 AN: 152084 Hom.: 62468 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.904 AC: 137595 AN: 152202 Hom.: 62519 Cov.: 31 AF XY: 0.903 AC XY: 67161 AN XY: 74410

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.906

Alfa AF: 0.881 Hom.: 133146

Bravo AF: 0.900

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.60

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: rs544368; hg19: chr11-124537995;