chr11-124637071-C-T

Variant names:

• chr11-124637071-C-T
• rs7941327
• NM_170601.5:c.1452G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_170601.5(SIAE):​c.1452G>A​(p.Thr484Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,613,918 control chromosomes in the GnomAD database, including 7,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3325 hom., cov: 32)
  • Exomes 𝑓: 0.037 (3890 hom.)
• Consequence: SIAE NM_170601.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.82
• Publications: 13 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-124637071-C-T is Benign according to our data. Variant chr11-124637071-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 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.1452G>A	p.Thr484Thr	synonymous	Exon 10 of 10	NP_733746.1	Q9HAT2-1
	SIAE	NM_001199922.2		c.1347G>A	p.Thr449Thr	synonymous	Exon 12 of 12	NP_001186851.1	Q9HAT2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAE	ENST00000263593.8	TSL:1 MANE Select	c.1452G>A	p.Thr484Thr	synonymous	Exon 10 of 10	ENSP00000263593.3	Q9HAT2-1
	SIAE	ENST00000618733.4	TSL:1	c.1347G>A	p.Thr449Thr	synonymous	Exon 12 of 12	ENSP00000478211.1	Q9HAT2-2
	SIAE	ENST00000899891.1		c.1443G>A	p.Thr481Thr	synonymous	Exon 10 of 10	ENSP00000569950.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19775 AN: 151908 Hom.: 3300 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.00576

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0545 AC: 13706 AN: 251460 AF XY: 0.0472

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.0338

Gnomad ASJ exome AF: 0.0390

Gnomad EAS exome AF: 0.102

Gnomad FIN exome AF: 0.00513

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0372 AC: 54455 AN: 1461890 Hom.: 3890 Cov.: 31 AF XY: 0.0361 AC XY: 26250 AN XY: 727246

African (AFR) AF: 0.409 AC: 13687 AN: 33480

American (AMR) AF: 0.0381 AC: 1706 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 1052 AN: 26136

East Asian (EAS) AF: 0.137 AC: 5420 AN: 39700

South Asian (SAS) AF: 0.0348 AC: 2999 AN: 86258

European-Finnish (FIN) AF: 0.00648 AC: 346 AN: 53420

Middle Eastern (MID) AF: 0.0319 AC: 184 AN: 5768

European-Non Finnish (NFE) AF: 0.0229 AC: 25479 AN: 1112008

Other (OTH) AF: 0.0593 AC: 3582 AN: 60396

GnomAD4 genome AF: 0.131 AC: 19850 AN: 152028 Hom.: 3325 Cov.: 32 AF XY: 0.126 AC XY: 9371 AN XY: 74326

African (AFR) AF: 0.391 AC: 16192 AN: 41368

American (AMR) AF: 0.0667 AC: 1020 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3466

East Asian (EAS) AF: 0.101 AC: 521 AN: 5152

South Asian (SAS) AF: 0.0378 AC: 182 AN: 4820

European-Finnish (FIN) AF: 0.00576 AC: 61 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1519 AN: 68014

Other (OTH) AF: 0.100 AC: 212 AN: 2116

Alfa AF: 0.0591 Hom.: 3735

Bravo AF: 0.148

Asia WGS AF: 0.121 AC: 421 AN: 3478

EpiCase AF: 0.0234

EpiControl AF: 0.0225

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SIAE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.12
DANN	Benign	0.81
PhyloP100		-1.8
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7941327; hg19: chr11-124506967; COSMIC: COSV52514648; COSMIC: COSV52514648;