11-124668099-T-C

Variant names:

• chr11-124668099-T-C
• rs544368
• NM_170601.5:c.229+1261A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170601.5(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 NM_170601.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 22 publications found

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]

SIAE Gene-Disease associations (from GenCC):

• autoimmune disease, susceptibility to, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170601.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	NM_170601.5	MANE Select	c.229+1261A>G		intron	N/A	NP_733746.1
	SIAE	NM_001199922.2		c.124+1261A>G		intron	N/A	NP_001186851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	ENST00000263593.8	TSL:1 MANE Select	c.229+1261A>G		intron	N/A	ENSP00000263593.3
	SIAE	ENST00000618733.4	TSL:1	c.124+1261A>G		intron	N/A	ENSP00000478211.1
	SIAE	ENST00000436137.2	TSL:1	n.342+1261A>G		intron	N/A

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

African (AFR) AF: 0.976 AC: 40528 AN: 41526

American (AMR) AF: 0.807 AC: 12329 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3300 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5174 AN: 5180

South Asian (SAS) AF: 0.924 AC: 4460 AN: 4828

European-Finnish (FIN) AF: 0.890 AC: 9423 AN: 10590

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59371 AN: 68012

Other (OTH) AF: 0.906 AC: 1910 AN: 2108

Alfa AF: 0.883 Hom.: 215600

Bravo AF: 0.900

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs544368; hg19: chr11-124537995;