17-46720454-A-G

Variant names:

• chr17-46720454-A-G
• rs12947457
• NM_006178.4:c.1762-6095A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006178.4(NSF):​c.1762-6095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,078 control chromosomes in the GnomAD database, including 3,515 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 (3515 hom., cov: 32)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• 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 rank	MANE	Protein	UniProt
NSF	NM_006178.4	c.1762-6095A>G		intron_variant	Intron 15 of 20	ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+169935A>G		intron_variant	Intron 10 of 10		XP_024306541.1
NSF	NR_040116.2	n.1829-6095A>G		intron_variant	Intron 14 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1762-6095A>G		intron_variant	Intron 15 of 20	1	NM_006178.4	ENSP00000381293.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23229 AN: 151962 Hom.: 3486 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.153 AC: 23308 AN: 152078 Hom.: 3515 Cov.: 32 AF XY: 0.158 AC XY: 11750 AN XY: 74358

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.0681

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0564 Hom.: 1406

Bravo AF: 0.180

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.79

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: rs12947457; hg19: chr17-44797820;