NM_080723.5:c.*1186G>A

Variant names:

• chr6-24147132-G-A
• rs9393530
• NM_080723.5:c.*1186G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NRSN1	NM_080723.5	c.*1186G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000378491.9	NP_542454.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRSN1	ENST00000378491.9	c.*1186G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_080723.5	ENSP00000367752.4
NRSN1	ENST00000378478.5	c.*1186G>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000367739.2
NRSN1	ENST00000468195.2	n.257-7639G>A		intron_variant	Intron 2 of 2	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00873 AC: 362 AN: 41480

American (AMR) AF: 0.0234 AC: 357 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00250 AC: 12 AN: 4806

European-Finnish (FIN) AF: 0.0971 AC: 1025 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0565 AC: 3839 AN: 67994

Other (OTH) AF: 0.0289 AC: 61 AN: 2112

Alfa AF: 0.0447 Hom.: 355

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
PhyloP100		2.6
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: rs9393530; hg19: chr6-24147360;