rs4793992

chr17-48930845-A-Gchr17-48930845-A-T

Variant summary

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

The NM_007241.4(SNF8):c.640-233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,170 control chromosomes in the GnomAD database, including 15,431 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 0.41 (15431 hom., cov: 33)
• Consequence: SNF8 NM_007241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

Genes affected

SNF8 (HGNC:17028): (SNF8 subunit of ESCRT-II) The protein encoded by this gene is a component of the endosomal sorting complex required for transport II (ESCRT-II), which regulates the movement of ubiquitinylated transmembrane proteins to the lysosome for degradation. This complex also interacts with the RNA polymerase II elongation factor (ELL) to overcome the repressive effects of ELL on RNA polymerase II activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

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 (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNF8	NM_007241.4	c.640-233T>C		intron_variant		ENST00000502492.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNF8	ENST00000502492.6	c.640-233T>C		intron_variant		1	NM_007241.4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62604 AN: 152052 Hom.: 15437 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.411 AC: 62593 AN: 152170 Hom.: 15431 Cov.: 33 AF XY: 0.415 AC XY: 30864 AN XY: 74384

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.441

Alfa AF: 0.472 Hom.: 5375

Bravo AF: 0.392

Asia WGS AF: 0.552 AC: 1915 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	5.1
Dann	Benign	0.68

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: rs4793992; hg19: chr17-47008207;