rs11958050

Variant names:

• chr5-138966139-A-G
• rs11958050
• NM_022464.5:c.768-14255T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-138966139-A-G
• chr5-138966139-A-T

Variant summary

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

The NM_022464.5(SIL1):​c.768-14255T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,896 control chromosomes in the GnomAD database, including 15,987 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 0.44 (15987 hom., cov: 31)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 13 publications found

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]

SIL1 Gene-Disease associations (from GenCC):

• Marinesco-Sjogren syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

LOC124901079 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5	c.768-14255T>C		intron_variant	Intron 7 of 9	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7	c.768-14255T>C		intron_variant	Intron 7 of 9	1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66602 AN: 151778 Hom.: 15947 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.439 AC: 66681 AN: 151896 Hom.: 15987 Cov.: 31 AF XY: 0.435 AC XY: 32319 AN XY: 74240

African (AFR) AF: 0.653 AC: 27002 AN: 41380

American (AMR) AF: 0.342 AC: 5229 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3466

East Asian (EAS) AF: 0.168 AC: 868 AN: 5160

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4806

European-Finnish (FIN) AF: 0.410 AC: 4322 AN: 10550

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24925 AN: 67946

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.389 Hom.: 9254

Bravo AF: 0.442

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.76
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: rs11958050; hg19: chr5-138301828;