rs4793992

Variant names:

• chr17-48930845-A-G
• rs4793992
• NM_007241.4:c.640-233T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-48930845-A-G
• chr17-48930845-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

SNF8 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 115

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder plus optic atrophy

  Inheritance: AR Classification: MODERATE Submitted by: G2P, PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007241.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNF8	NM_007241.4	MANE Select	c.640-233T>C		intron	N/A	NP_009172.2
	SNF8	NM_001317192.2		c.637-233T>C		intron	N/A	NP_001304121.1	Q96H20-2
	SNF8	NM_001317193.2		c.589-233T>C		intron	N/A	NP_001304122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNF8	ENST00000502492.6	TSL:1 MANE Select	c.640-233T>C		intron	N/A	ENSP00000421380.1	Q96H20-1
	SNF8	ENST00000290330.7	TSL:1	c.637-233T>C		intron	N/A	ENSP00000290330.3	Q96H20-2
	SNF8	ENST00000956813.1		c.727-233T>C		intron	N/A	ENSP00000626872.1

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

African (AFR) AF: 0.131 AC: 5435 AN: 41524

American (AMR) AF: 0.413 AC: 6311 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1759 AN: 3466

East Asian (EAS) AF: 0.710 AC: 3678 AN: 5180

South Asian (SAS) AF: 0.507 AC: 2443 AN: 4822

European-Finnish (FIN) AF: 0.542 AC: 5742 AN: 10588

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35628 AN: 67988

Other (OTH) AF: 0.441 AC: 931 AN: 2112

Alfa AF: 0.489 Hom.: 9560

Bravo AF: 0.392

Asia WGS AF: 0.552 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.68
PhyloP100		-0.62
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: rs4793992; hg19: chr17-47008207;