rs9393530

Positions:

• chr6-24147132-G-A

Variant summary

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

The NM_080723.5(NRSN1):​c.*1186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,072 control chromosomes in the GnomAD database, including 177 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 0.038 (177 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRSN1 NM_080723.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

Genes affected

NRSN1 (HGNC:17881): (neurensin 1) Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRSN1	NM_080723.5	c.*1186G>A		3_prime_UTR_variant	4/4	ENST00000378491.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRSN1	ENST00000378491.9	c.*1186G>A		3_prime_UTR_variant	4/4	1	NM_080723.5	P1
NRSN1	ENST00000378478.5	c.*1186G>A		3_prime_UTR_variant	4/4	1		P1
NRSN1	ENST00000468195.2	n.257-7639G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5768 AN: 151954 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.00875

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0971

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0292

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0379 AC: 5766 AN: 152072 Hom.: 177 Cov.: 32 AF XY: 0.0383 AC XY: 2850 AN XY: 74322

Gnomad4 AFR AF: 0.00873

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00250

Gnomad4 FIN AF: 0.0971

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0467 Hom.: 265

Bravo AF: 0.0310

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.3
DANN	Benign	0.66

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: rs9393530; hg19: chr6-24147360;