ENST00000509935.2:c.778-16872G>A

Variant names:

• chr5-65843936-G-A
• rs6892230
• ENST00000509935.2:c.778-16872G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0932 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.778-16872G>A		intron	N/A	ENSP00000426959.2

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

African (AFR) AF: 0.0957 AC: 3972 AN: 41498

American (AMR) AF: 0.0338 AC: 516 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0850 AC: 409 AN: 4812

European-Finnish (FIN) AF: 0.0231 AC: 244 AN: 10584

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3009 AN: 68006

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0552 Hom.: 39

Bravo AF: 0.0572

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs6892230; hg19: chr5-65139764;