rs1994970

Variant names:

• chr17-48936765-T-C
• rs1994970
• NM_007241.4:c.349+255A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-48936765-T-C
• chr17-48936765-T-A
• chr17-48936765-T-G

Variant summary

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

The NM_007241.4(SNF8):​c.349+255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 524,328 control chromosomes in the GnomAD database, including 67,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (15409 hom., cov: 31)
  • Exomes 𝑓: 0.52 (52203 hom.)
• Consequence: SNF8 NM_007241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 18 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

ENSG00000230532 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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.349+255A>G		intron	N/A	NP_009172.2
	SNF8	NM_001317192.2		c.349+255A>G		intron	N/A	NP_001304121.1	Q96H20-2
	SNF8	NM_001317193.2		c.298+255A>G		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.349+255A>G		intron	N/A	ENSP00000421380.1	Q96H20-1
	SNF8	ENST00000290330.7	TSL:1	c.349+255A>G		intron	N/A	ENSP00000290330.3	Q96H20-2
	SNF8	ENST00000956813.1		c.436+255A>G		intron	N/A	ENSP00000626872.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62574 AN: 151892 Hom.: 15415 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.507

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: 0.436

GnomAD4 exome AF: 0.518 AC: 193029 AN: 372318 Hom.: 52203 Cov.: 2 AF XY: 0.519 AC XY: 101456 AN XY: 195534

African (AFR) AF: 0.131 AC: 1452 AN: 11118

American (AMR) AF: 0.431 AC: 6098 AN: 14134

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 6022 AN: 11728

East Asian (EAS) AF: 0.720 AC: 18673 AN: 25942

South Asian (SAS) AF: 0.490 AC: 17516 AN: 35744

European-Finnish (FIN) AF: 0.536 AC: 12514 AN: 23346

Middle Eastern (MID) AF: 0.472 AC: 788 AN: 1668

European-Non Finnish (NFE) AF: 0.525 AC: 119176 AN: 226808

Other (OTH) AF: 0.494 AC: 10790 AN: 21830

GnomAD4 genome AF: 0.412 AC: 62563 AN: 152010 Hom.: 15409 Cov.: 31 AF XY: 0.415 AC XY: 30832 AN XY: 74274

African (AFR) AF: 0.132 AC: 5477 AN: 41504

American (AMR) AF: 0.413 AC: 6308 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1761 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3666 AN: 5164

South Asian (SAS) AF: 0.507 AC: 2437 AN: 4808

European-Finnish (FIN) AF: 0.542 AC: 5727 AN: 10566

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

European-Non Finnish (NFE) AF: 0.524 AC: 35598 AN: 67916

Other (OTH) AF: 0.440 AC: 924 AN: 2102

Alfa AF: 0.434 Hom.: 3144

Bravo AF: 0.393

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	-0.89
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.46
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: rs1994970; hg19: chr17-47014127;