rs12202381

Positions:

• chr6-24139714-A-G

Variant summary

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

The NM_080723.5(NRSN1):​c.189+5198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,212 control chromosomes in the GnomAD database, including 1,911 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 0.14 (1911 hom., cov: 32)
• Consequence: NRSN1 NM_080723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

NRSN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRSN1	NM_080723.5	c.189+5198A>G		intron_variant		ENST00000378491.9	NP_542454.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRSN1	ENST00000378491.9	c.189+5198A>G		intron_variant		1	NM_080723.5	ENSP00000367752.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21694 AN: 152094 Hom.: 1905 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.143 AC: 21712 AN: 152212 Hom.: 1911 Cov.: 32 AF XY: 0.137 AC XY: 10218 AN XY: 74430

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.165

Alfa AF: 0.120 Hom.: 1751

Bravo AF: 0.154

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.20

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: rs12202381; hg19: chr6-24139942;