rs183211

Positions:

• chr17-46710944-G-A
• chr17-46710944-G-C
• chr17-46710944-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006178.4(NSF):​c.1471-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,567,776 control chromosomes in the GnomAD database, including 58,456 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 (7704 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50752 hom.)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSF	NM_006178.4	c.1471-19G>A		intron_variant		ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+160425G>A		intron_variant			XP_024306541.1
NSF	NR_040116.2	n.1538-19G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1471-19G>A		intron_variant		1	NM_006178.4	ENSP00000381293.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45826 AN: 151970 Hom.: 7675 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.312

GnomAD3 exomes AF: 0.278 AC: 57912 AN: 208432 Hom.: 10185 AF XY: 0.263 AC XY: 30021 AN XY: 114208

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.602

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.251 AC: 355364 AN: 1415688 Hom.: 50752 Cov.: 32 AF XY: 0.247 AC XY: 173889 AN XY: 703696

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.302 AC: 45899 AN: 152088 Hom.: 7704 Cov.: 32 AF XY: 0.297 AC XY: 22112 AN XY: 74338

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.310

Alfa AF: 0.250 Hom.: 7535

Bravo AF: 0.335

Asia WGS AF: 0.382 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.6
DANN	Benign	0.60

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: rs183211; hg19: chr17-44788310;