rs929775

Positions:

• chr5-139188987-A-C
• chr5-139188987-A-T

Variant summary

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

The NM_022464.5(SIL1):​c.-11+9282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,068 control chromosomes in the GnomAD database, including 17,877 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 0.48 (17877 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIL1	NM_022464.5	c.-11+9282T>G		intron_variant		ENST00000394817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIL1	ENST00000394817.7	c.-11+9282T>G		intron_variant		1	NM_022464.5	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72473 AN: 151950 Hom.: 17853 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.477 AC: 72534 AN: 152068 Hom.: 17877 Cov.: 32 AF XY: 0.476 AC XY: 35425 AN XY: 74348

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.478

Alfa AF: 0.476 Hom.: 6070

Bravo AF: 0.461

Asia WGS AF: 0.350 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.73

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: rs929775; hg19: chr5-138524676;