rs199455

Positions:

• chr17-46721850-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

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

LRRC37A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSF	NM_006178.4	c.1762-4699C>T		intron_variant		ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+171331C>T		intron_variant			XP_024306541.1
NSF	NR_040116.2	n.1829-4699C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1762-4699C>T		intron_variant		1	NM_006178.4	ENSP00000381293	P3
RPS7P11	ENST00000484240.1	n.318G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.694

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.841

Gnomad4 FIN exome AF: 0.847

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.708

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

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.642

Alfa AF: 0.701 Hom.: 4842

Bravo AF: 0.591

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

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