5-139146817-G-T

Variant names:

• chr5-139146817-G-T
• rs7721110
• NM_022464.5:c.-10-18964C>A

Variant summary

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

The NM_022464.5(SIL1):​c.-10-18964C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,948 control chromosomes in the GnomAD database, including 23,296 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 0.54 (23296 hom., cov: 31)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIL1	NM_022464.5	c.-10-18964C>A		intron_variant	Intron 1 of 9	ENST00000394817.7	NP_071909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIL1	ENST00000394817.7	c.-10-18964C>A		intron_variant	Intron 1 of 9	1	NM_022464.5	ENSP00000378294.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81715 AN: 151832 Hom.: 23253 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.538 AC: 81807 AN: 151948 Hom.: 23296 Cov.: 31 AF XY: 0.533 AC XY: 39587 AN XY: 74274

African (AFR) AF: 0.721 AC: 29896 AN: 41456

American (AMR) AF: 0.447 AC: 6814 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3468

East Asian (EAS) AF: 0.179 AC: 922 AN: 5154

South Asian (SAS) AF: 0.411 AC: 1976 AN: 4812

European-Finnish (FIN) AF: 0.521 AC: 5497 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33335 AN: 67944

Other (OTH) AF: 0.514 AC: 1083 AN: 2106

Alfa AF: 0.458 Hom.: 1719

Bravo AF: 0.538

Asia WGS AF: 0.338 AC: 1173 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.29
PhyloP100		-0.071
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: rs7721110; hg19: chr5-138482506;