rs7216231

Positions:

• chr17-46738377-A-G

Variant summary

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

The ENST00000398238.8(NSF):​c.1908+9443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,144 control chromosomes in the GnomAD database, including 50,404 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 0.78 (50404 hom., cov: 32)
• Consequence: NSF ENST00000398238.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSF	NM_006178.4	c.1908+9443A>G		intron_variant		ENST00000398238.8	NP_006169.2
LRRC37A2	XM_024450773.2	c.4809+187858A>G		intron_variant			XP_024306541.1
NSF	NR_040116.2	n.1975+9443A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8	c.1908+9443A>G		intron_variant		1	NM_006178.4	ENSP00000381293	P3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119099 AN: 152026 Hom.: 50407 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.783 AC: 119114 AN: 152144 Hom.: 50404 Cov.: 32 AF XY: 0.779 AC XY: 57967 AN XY: 74420

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.824

Alfa AF: 0.879 Hom.: 22620

Bravo AF: 0.747

Asia WGS AF: 0.632 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.76

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: rs7216231; hg19: chr17-44815743;