rs16894446

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509935.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLN	ENST00000509935.2	TSL:5	c.778-19175C>T		intron	N/A	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

African (AFR) AF: 0.00902 AC: 375 AN: 41568

American (AMR) AF: 0.113 AC: 1734 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1707 AN: 5184

South Asian (SAS) AF: 0.114 AC: 551 AN: 4814

European-Finnish (FIN) AF: 0.0192 AC: 204 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1653 AN: 68022

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0393 Hom.: 858

Bravo AF: 0.0516

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.20
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs16894446; hg19: chr5-65137461;