NM_020726.5:c.1980+2570A>G

Variant names:

• chr5-65814961-A-G
• rs895379
• NM_020726.5:c.1980+2570A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020726.5(NLN):​c.1980+2570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,972 control chromosomes in the GnomAD database, including 19,082 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 0.49 (19082 hom., cov: 32)
• Consequence: NLN NM_020726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLN	NM_020726.5	c.1980+2570A>G		intron_variant	Intron 12 of 12	ENST00000380985.10	NP_065777.1
NLN	XM_005248559.4	c.1926+2570A>G		intron_variant	Intron 12 of 12		XP_005248616.1
NLN	XM_047417443.1	c.1911+2570A>G		intron_variant	Intron 12 of 12		XP_047273399.1
NLN	XM_047417444.1	c.1911+2570A>G		intron_variant	Intron 12 of 12		XP_047273400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000380985.10	c.1980+2570A>G		intron_variant	Intron 12 of 12	1	NM_020726.5	ENSP00000370372.5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74932 AN: 151854 Hom.: 19079 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.493 AC: 74966 AN: 151972 Hom.: 19082 Cov.: 32 AF XY: 0.494 AC XY: 36655 AN XY: 74274

African (AFR) AF: 0.384 AC: 15922 AN: 41448

American (AMR) AF: 0.496 AC: 7572 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1804 AN: 5166

South Asian (SAS) AF: 0.418 AC: 2018 AN: 4824

European-Finnish (FIN) AF: 0.599 AC: 6306 AN: 10532

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.555 AC: 37727 AN: 67950

Other (OTH) AF: 0.478 AC: 1007 AN: 2108

Alfa AF: 0.520 Hom.: 19850

Bravo AF: 0.480

Asia WGS AF: 0.343 AC: 1194 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.77
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs895379; hg19: chr5-65110789;