17-46738766-G-T

Position:

• chr17-46738766-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.1908+9832G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,208 control chromosomes in the GnomAD database, including 3,475 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 0.15 (3475 hom., cov: 32)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSF	NM_006178.4	c.1908+9832G>T		intron_variant		ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+188247G>T		intron_variant			XP_024306541.1
NSF	NR_040116.2	n.1975+9832G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1908+9832G>T		intron_variant		1	NM_006178.4	ENSP00000381293	P3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23079 AN: 152090 Hom.: 3445 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.152 AC: 23160 AN: 152208 Hom.: 3475 Cov.: 32 AF XY: 0.157 AC XY: 11690 AN XY: 74432

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0607 Hom.: 436

Bravo AF: 0.178

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.93
DANN	Benign	0.65

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: rs12325819; hg19: chr17-44816132;