6-6004726-G-C

Position:

• chr6-6004726-G-C

Variant summary

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

The NM_016588.3(NRN1):​c.55+1969C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,028 control chromosomes in the GnomAD database, including 16,756 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 0.45 (16756 hom., cov: 32)
• Consequence: NRN1 NM_016588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRN1	NM_016588.3	c.55+1969C>G		intron_variant		ENST00000244766.7	NP_057672.1
NRN1	NM_001278710.2	c.55+1969C>G		intron_variant			NP_001265639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRN1	ENST00000244766.7	c.55+1969C>G		intron_variant		1	NM_016588.3	ENSP00000244766.2
NRN1	ENST00000616243.1	c.55+1969C>G		intron_variant		4		ENSP00000484055.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69039 AN: 151910 Hom.: 16712 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.455 AC: 69147 AN: 152028 Hom.: 16756 Cov.: 32 AF XY: 0.462 AC XY: 34374 AN XY: 74326

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.453

Alfa AF: 0.421 Hom.: 1763

Bravo AF: 0.468

Asia WGS AF: 0.646 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.68
DANN	Benign	0.47

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: rs645649; hg19: chr6-6004959;