rs10468274

Variant names:

• chr16-67888439-G-A
• rs10468274
• NM_001348682.2:c.213-228G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001348682.2(NRN1L):​c.213-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,972 control chromosomes in the GnomAD database, including 10,382 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 0.30 (10382 hom., cov: 31)
• Consequence: NRN1L NM_001348682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 23 publications found

Genes affected

NRN1L (HGNC:29811): (neuritin 1 like) The protein encoded by this gene is extracellular and enhances both neurite growth and neuronal survival. The encoded protein is found both as a GPI anchored membrane-bound form and as a secreted form. This activity-related ligand functions as a homodimer or heterodimer. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRN1L	NM_001348682.2	c.213-228G>A		intron_variant	Intron 2 of 2		NP_001335611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRN1L	ENST00000576758.1	c.207-228G>A		intron_variant	Intron 2 of 2	2		ENSP00000459748.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46163 AN: 151854 Hom.: 10346 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.304 AC: 46249 AN: 151972 Hom.: 10382 Cov.: 31 AF XY: 0.301 AC XY: 22393 AN XY: 74294

African (AFR) AF: 0.635 AC: 26285 AN: 41402

American (AMR) AF: 0.236 AC: 3604 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.0313 AC: 162 AN: 5180

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4814

European-Finnish (FIN) AF: 0.189 AC: 1996 AN: 10572

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11591 AN: 67968

Other (OTH) AF: 0.276 AC: 581 AN: 2106

Alfa AF: 0.209 Hom.: 14296

Bravo AF: 0.318

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.89
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs10468274; hg19: chr16-67922342;