6-6007758-G-C

Variant names:

• chr6-6007758-G-C
• rs582262
• NM_001278710.2:c.-306C>G

Variant summary

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

The NM_001278710.2(NRN1):​c.-306C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,110 control chromosomes in the GnomAD database, including 13,665 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 0.40 (13665 hom., cov: 33)
• Consequence: NRN1 NM_001278710.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

Genes affected

NRN1 (HGNC:17972): (neuritin 1) This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRN1	NM_001278710.2	c.-306C>G		upstream_gene_variant			NP_001265639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRN1	ENST00000616243.1	c.-306C>G		upstream_gene_variant		4		ENSP00000484055.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60928 AN: 151992 Hom.: 13619 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.401 AC: 61034 AN: 152110 Hom.: 13665 Cov.: 33 AF XY: 0.406 AC XY: 30160 AN XY: 74348

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.378

Alfa AF: 0.206 Hom.: 417

Bravo AF: 0.419

Asia WGS AF: 0.511 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs582262; hg19: chr6-6007991;