NM_006178.4:c.1908+2060G>A

Variant names:

• chr17-46730994-G-A
• rs35937770
• NM_006178.4:c.1908+2060G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006178.4(NSF):​c.1908+2060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,996 control chromosomes in the GnomAD database, including 5,836 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 0.25 (5836 hom., cov: 32)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 17 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSF	NM_006178.4	c.1908+2060G>A		intron_variant	Intron 17 of 20	ENST00000398238.8	NP_006169.2
NSF	NR_040116.2	n.1975+2060G>A		intron_variant	Intron 16 of 19
LRRC37A2	XM_024450773.2	c.4809+180475G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1908+2060G>A		intron_variant	Intron 17 of 20	1	NM_006178.4	ENSP00000381293.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37685 AN: 151880 Hom.: 5827 Cov.: 32

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.248 AC: 37700 AN: 151996 Hom.: 5836 Cov.: 32 AF XY: 0.254 AC XY: 18889 AN XY: 74286

African (AFR) AF: 0.0587 AC: 2433 AN: 41478

American (AMR) AF: 0.250 AC: 3826 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1538 AN: 5170

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4822

European-Finnish (FIN) AF: 0.446 AC: 4698 AN: 10542

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22286 AN: 67932

Other (OTH) AF: 0.246 AC: 520 AN: 2110

Alfa AF: 0.304 Hom.: 6146

Bravo AF: 0.224

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.45
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs35937770; hg19: chr17-44808360;