rs7216231

Variant names:

• chr17-46738377-A-G
• rs7216231
• NM_006178.4:c.1908+9443A>G

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+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 NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 7 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=-0.9).
• 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 rank	MANE	Protein	UniProt
NSF	NM_006178.4	c.1908+9443A>G		intron_variant	Intron 17 of 20	ENST00000398238.8	NP_006169.2
NSF	NR_040116.2	n.1975+9443A>G		intron_variant	Intron 16 of 19
LRRC37A2	XM_024450773.2	c.4809+187858A>G		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+9443A>G		intron_variant	Intron 17 of 20	1	NM_006178.4	ENSP00000381293.4

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

African (AFR) AF: 0.483 AC: 20029 AN: 41456

American (AMR) AF: 0.736 AC: 11251 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3168 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2042 AN: 5164

South Asian (SAS) AF: 0.875 AC: 4221 AN: 4824

European-Finnish (FIN) AF: 0.928 AC: 9842 AN: 10604

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65733 AN: 68020

Other (OTH) AF: 0.824 AC: 1738 AN: 2110

Alfa AF: 0.877 Hom.: 35789

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
PhyloP100		0.068
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: rs7216231; hg19: chr17-44815743;