17-46710944-G-A

Variant names:

• chr17-46710944-G-A
• rs183211
• NM_006178.4:c.1471-19G>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.1471-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,567,776 control chromosomes in the GnomAD database, including 58,456 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 0.30 (7704 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50752 hom.)
• Consequence: NSF NM_006178.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 104 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006178.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	NM_006178.4	MANE Select	c.1471-19G>A		intron	N/A	NP_006169.2
	NSF	NR_040116.2		n.1538-19G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSF	ENST00000398238.8	TSL:1 MANE Select	c.1471-19G>A		intron	N/A	ENSP00000381293.4
	NSF	ENST00000465370.2	TSL:5	c.1471-19G>A		intron	N/A	ENSP00000467779.2
	NSF	ENST00000706392.1		c.1471-19G>A		intron	N/A	ENSP00000516369.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45826 AN: 151970 Hom.: 7675 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.312

GnomAD2 exomes AF: 0.278 AC: 57912 AN: 208432 AF XY: 0.263

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.602

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.251 AC: 355364 AN: 1415688 Hom.: 50752 Cov.: 32 AF XY: 0.247 AC XY: 173889 AN XY: 703696

African (AFR) AF: 0.396 AC: 12042 AN: 30424

American (AMR) AF: 0.480 AC: 15442 AN: 32182

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7176 AN: 25052

East Asian (EAS) AF: 0.667 AC: 24508 AN: 36766

South Asian (SAS) AF: 0.157 AC: 12208 AN: 77750

European-Finnish (FIN) AF: 0.153 AC: 8154 AN: 53164

Middle Eastern (MID) AF: 0.270 AC: 1333 AN: 4934

European-Non Finnish (NFE) AF: 0.236 AC: 258720 AN: 1096856

Other (OTH) AF: 0.269 AC: 15781 AN: 58560

GnomAD4 genome AF: 0.302 AC: 45899 AN: 152088 Hom.: 7704 Cov.: 32 AF XY: 0.297 AC XY: 22112 AN XY: 74338

African (AFR) AF: 0.389 AC: 16132 AN: 41468

American (AMR) AF: 0.408 AC: 6234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3468

East Asian (EAS) AF: 0.607 AC: 3132 AN: 5164

South Asian (SAS) AF: 0.182 AC: 875 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1518 AN: 10590

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

European-Non Finnish (NFE) AF: 0.235 AC: 15991 AN: 67986

Other (OTH) AF: 0.310 AC: 654 AN: 2108

Alfa AF: 0.264 Hom.: 20515

Bravo AF: 0.335

Asia WGS AF: 0.382 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.6
DANN	Benign	0.60
PhyloP100		1.0
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: rs183211; hg19: chr17-44788310; COSMIC: COSV107307408; COSMIC: COSV107307408;