17-46717868-A-G

Variant names:

• chr17-46717868-A-G
• rs142167
• NM_006178.4:c.1761+3882A>G

Variant summary

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

The NM_006178.4(NSF):​c.1761+3882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,036 control chromosomes in the GnomAD database, including 7,688 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 0.30 (7688 hom., cov: 32)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 37 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]

LOC107985026 (HGNC:):

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	NM_006178.4	MANE Select	c.1761+3882A>G		intron	N/A	NP_006169.2
	NSF	NR_040116.2		n.1828+3882A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.1761+3882A>G		intron	N/A	ENSP00000381293.4
	NSF	ENST00000465370.2	TSL:5	c.1761+3882A>G		intron	N/A	ENSP00000467779.2
	NSF	ENST00000706392.1		c.1761+3882A>G		intron	N/A	ENSP00000516369.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45769 AN: 151918 Hom.: 7659 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.302 AC: 45842 AN: 152036 Hom.: 7688 Cov.: 32 AF XY: 0.297 AC XY: 22065 AN XY: 74290

African (AFR) AF: 0.388 AC: 16083 AN: 41430

American (AMR) AF: 0.408 AC: 6231 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3472

East Asian (EAS) AF: 0.605 AC: 3126 AN: 5166

South Asian (SAS) AF: 0.182 AC: 876 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1510 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15994 AN: 67966

Other (OTH) AF: 0.311 AC: 657 AN: 2114

Alfa AF: 0.284 Hom.: 5172

Bravo AF: 0.335

Asia WGS AF: 0.382 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.41
PhyloP100		-0.24
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: rs142167; hg19: chr17-44795234; COSMIC: COSV56573752; COSMIC: COSV56573752;