rs6892230

Positions:

• chr5-65843936-G-A

Variant summary

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

The ENST00000509935.2(NLN):​c.778-16872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,146 control chromosomes in the GnomAD database, including 312 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 0.055 (312 hom., cov: 31)
• Consequence: NLN ENST00000509935.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

Genes affected

NLN (HGNC:16058): (neurolysin) This gene encodes a member of the metallopeptidase M3 protein family that cleaves neurotensin at the Pro10-Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13). The encoded protein is likely involved in the termination of the neurotensinergic signal in the central nervous system and in the gastrointestinal tract.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000509935.2	c.778-16872G>A		intron_variant		5		ENSP00000426959

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8428 AN: 152028 Hom.: 312 Cov.: 31

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0555 AC: 8440 AN: 152146 Hom.: 312 Cov.: 31 AF XY: 0.0542 AC XY: 4034 AN XY: 74378

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0535 Hom.: 35

Bravo AF: 0.0572

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
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: rs6892230; hg19: chr5-65139764;