rs7226263

Variant names:

• chr17-46737518-T-C
• rs7226263
• NM_006178.4:c.1908+8584T>C

Variant summary

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

The NM_006178.4(NSF):​c.1908+8584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,762 control chromosomes in the GnomAD database, including 50,294 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 0.78 (50294 hom., cov: 28)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 8 publications found

Genes affected

NSF (HGNC:8016): (N-ethylmaleimide sensitive factor, vesicle fusing ATPase) Enables PDZ domain binding activity and ionotropic glutamate receptor binding activity. Involved in intracellular protein transport; positive regulation of protein catabolic process; and positive regulation of receptor recycling. Located in Golgi apparatus; cytosol; and plasma membrane. Implicated in developmental and epileptic encephalopathy. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006178.4. 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
	NSF	NM_006178.4	MANE Select	c.1908+8584T>C		intron	N/A	NP_006169.2
	NSF	NR_040116.2		n.1975+8584T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.1908+8584T>C		intron	N/A	ENSP00000381293.4
	NSF	ENST00000465370.2	TSL:5	c.1908+8584T>C		intron	N/A	ENSP00000467779.2
	NSF	ENST00000706392.1		c.1908+8584T>C		intron	N/A	ENSP00000516369.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118808 AN: 151644 Hom.: 50297 Cov.: 28

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.783 AC: 118823 AN: 151762 Hom.: 50294 Cov.: 28 AF XY: 0.779 AC XY: 57752 AN XY: 74134

African (AFR) AF: 0.482 AC: 19926 AN: 41304

American (AMR) AF: 0.736 AC: 11223 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3163 AN: 3462

East Asian (EAS) AF: 0.395 AC: 2032 AN: 5138

South Asian (SAS) AF: 0.876 AC: 4202 AN: 4798

European-Finnish (FIN) AF: 0.928 AC: 9774 AN: 10530

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65677 AN: 67964

Other (OTH) AF: 0.824 AC: 1736 AN: 2108

Alfa AF: 0.921 Hom.: 36441

Bravo AF: 0.747

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.34
PhyloP100		-0.58
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: rs7226263; hg19: chr17-44814884;