17-46721850-C-T

Variant names:

• chr17-46721850-C-T
• rs199455
• NM_006178.4:c.1762-4699C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006178.4(NSF):​c.1762-4699C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,542 control chromosomes in the GnomAD database, including 32,771 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 0.63 (32771 hom., cov: 29)
  • Exomes 𝑓: 0.73 (393452 hom.)
  • Failed GnomAD Quality Control
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 32 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]

RPS7P11 (HGNC:35841): (ribosomal protein S7 pseudogene 11)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 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.1762-4699C>T		intron	N/A	NP_006169.2
	NSF	NR_040116.2		n.1829-4699C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.1762-4699C>T		intron	N/A	ENSP00000381293.4
	NSF	ENST00000465370.2	TSL:5	c.1762-4699C>T		intron	N/A	ENSP00000467779.2
	NSF	ENST00000706392.1		c.1762-4699C>T		intron	N/A	ENSP00000516369.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96041 AN: 151422 Hom.: 32766 Cov.: 29

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.640

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.735 AC: 1046757 AN: 1424528 Hom.: 393452 Cov.: 28 AF XY: 0.740 AC XY: 526426 AN XY: 710970

African (AFR) AF: 0.378 AC: 12479 AN: 33020

American (AMR) AF: 0.493 AC: 22024 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 18002 AN: 25934

East Asian (EAS) AF: 0.336 AC: 13304 AN: 39594

South Asian (SAS) AF: 0.841 AC: 71872 AN: 85486

European-Finnish (FIN) AF: 0.847 AC: 45207 AN: 53402

Middle Eastern (MID) AF: 0.701 AC: 3922 AN: 5598

European-Non Finnish (NFE) AF: 0.759 AC: 818067 AN: 1077696

Other (OTH) AF: 0.708 AC: 41880 AN: 59132

GnomAD4 genome AF: 0.634 AC: 96064 AN: 151542 Hom.: 32771 Cov.: 29 AF XY: 0.639 AC XY: 47297 AN XY: 74002

African (AFR) AF: 0.393 AC: 16193 AN: 41208

American (AMR) AF: 0.563 AC: 8559 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2428 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2030 AN: 5146

South Asian (SAS) AF: 0.817 AC: 3919 AN: 4798

European-Finnish (FIN) AF: 0.856 AC: 9004 AN: 10514

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51790 AN: 67918

Other (OTH) AF: 0.642 AC: 1343 AN: 2092

Alfa AF: 0.688 Hom.: 4889

Bravo AF: 0.591

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		2.5
Mutation Taster		=86/14	polymorphism

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: rs199455; hg19: chr17-44799216; COSMIC: COSV56574776; COSMIC: COSV56574776;