5-138955716-A-G

Position:

• chr5-138955716-A-G

Variant summary

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

The NM_022464.5(SIL1):​c.768-3832T>C 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 152,094 control chromosomes in the GnomAD database, including 14,139 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 (14139 hom., cov: 33)
• Consequence: SIL1 NM_022464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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]

LOC124901079 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIL1	NM_022464.5	c.768-3832T>C		intron_variant		ENST00000394817.7
LOC124901079	XR_007058954.1	n.3835A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIL1	ENST00000394817.7	c.768-3832T>C		intron_variant		1	NM_022464.5	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63267 AN: 151976 Hom.: 14105 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.416 AC: 63342 AN: 152094 Hom.: 14139 Cov.: 33 AF XY: 0.413 AC XY: 30662 AN XY: 74330

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.377

Alfa AF: 0.384 Hom.: 6417

Bravo AF: 0.420

Asia WGS AF: 0.246 AC: 855 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	1.9
DANN	Benign	0.32

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: rs7717375; hg19: chr5-138291405;