rs10045761

Positions:

• chr5-139061600-G-A
• chr5-139061600-G-C

Variant summary

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

The NM_022464.5(SIL1):​c.245-10554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,068 control chromosomes in the GnomAD database, including 14,574 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 (14574 hom., cov: 32)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIL1	NM_022464.5	c.245-10554C>T		intron_variant		ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7	c.245-10554C>T		intron_variant		1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64368 AN: 151950 Hom.: 14546 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.424 AC: 64441 AN: 152068 Hom.: 14574 Cov.: 32 AF XY: 0.419 AC XY: 31139 AN XY: 74328

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.390

Alfa AF: 0.314 Hom.: 1113

Bravo AF: 0.427

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.6
DANN	Benign	0.86

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: rs10045761; hg19: chr5-138397289;