rs11748097

chr5-139144198-C-A

Variant summary

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

The NM_022464.5(SIL1):c.-10-16345G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,096 control chromosomes in the GnomAD database, including 6,442 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 0.27 (6442 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIL1	NM_022464.5	c.-10-16345G>T		intron_variant		ENST00000394817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIL1	ENST00000394817.7	c.-10-16345G>T		intron_variant		1	NM_022464.5	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41827 AN: 151976 Hom.: 6452 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.275 AC: 41814 AN: 152096 Hom.: 6442 Cov.: 32 AF XY: 0.275 AC XY: 20444 AN XY: 74334

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.270

Alfa AF: 0.319 Hom.: 1039

Bravo AF: 0.260

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	13
Dann	Benign	0.93

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: rs11748097; hg19: chr5-138479887;