rs16894446

Variant names:

• chr5-65841633-C-T
• rs16894446
• ENST00000509935.2:c.778-19175C>T

Variant summary

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

The ENST00000509935.2(NLN):​c.778-19175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,286 control chromosomes in the GnomAD database, including 495 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 0.042 (495 hom., cov: 32)
• Consequence: NLN ENST00000509935.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000509935.2	c.778-19175C>T		intron_variant	Intron 5 of 6	5		ENSP00000426959.2

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6395 AN: 152168 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.00905

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0421 AC: 6413 AN: 152286 Hom.: 495 Cov.: 32 AF XY: 0.0456 AC XY: 3397 AN XY: 74462

Gnomad4 AFR AF: 0.00902

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0419 Hom.: 353

Bravo AF: 0.0516

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16894446; hg19: chr5-65137461;