rs1433008

Variant names:

• chr5-138997975-T-C
• rs1433008
• NM_022464.5:c.767+23196A>G

Variant summary

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

The NM_022464.5(SIL1):​c.767+23196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,018 control chromosomes in the GnomAD database, including 13,894 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 0.42 (13894 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 1 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5	c.767+23196A>G		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.767+23196A>G		intron_variant	Intron 7 of 9	1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63126 AN: 151900 Hom.: 13867 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.416 AC: 63195 AN: 152018 Hom.: 13894 Cov.: 32 AF XY: 0.411 AC XY: 30565 AN XY: 74312

African (AFR) AF: 0.572 AC: 23700 AN: 41424

American (AMR) AF: 0.346 AC: 5281 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3470

East Asian (EAS) AF: 0.145 AC: 751 AN: 5180

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4814

European-Finnish (FIN) AF: 0.366 AC: 3861 AN: 10552

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25187 AN: 67982

Other (OTH) AF: 0.387 AC: 818 AN: 2114

Alfa AF: 0.406 Hom.: 1774

Bravo AF: 0.418

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.0
DANN	Benign	0.35
PhyloP100		0.20
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: rs1433008; hg19: chr5-138333664;