rs11957633

chr5-139028705-T-C

Variant summary

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

The NM_022464.5(SIL1):c.454-1713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,112 control chromosomes in the GnomAD database, including 6,053 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 0.26 (6053 hom., cov: 31)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

Genes affected

SIL1 (HGNC:24624): (SIL1 nucleotide exchange factor) This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIL1	NM_022464.5	c.454-1713A>G		intron_variant		ENST00000394817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIL1	ENST00000394817.7	c.454-1713A>G		intron_variant		1	NM_022464.5	P1
	ENST00000512875.2	n.446-4189T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39542 AN: 151992 Hom.: 6062 Cov.: 31

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.260 AC: 39527 AN: 152112 Hom.: 6053 Cov.: 31 AF XY: 0.260 AC XY: 19360 AN XY: 74340

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.261

Alfa AF: 0.307 Hom.: 990

Bravo AF: 0.245

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.50
Dann	Benign	0.58

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: rs11957633; hg19: chr5-138364394;