rs2561196

Variant names:

• chr5-65809795-G-A
• rs2561196
• NM_020726.5:c.1714+94G>A

Variant summary

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

The NM_020726.5(NLN):​c.1714+94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,098,836 control chromosomes in the GnomAD database, including 270,748 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 0.72 (39861 hom., cov: 32)
  • Exomes 𝑓: 0.70 (230887 hom.)
• Consequence: NLN NM_020726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLN	NM_020726.5	c.1714+94G>A		intron_variant	Intron 10 of 12	ENST00000380985.10	NP_065777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000380985.10	c.1714+94G>A		intron_variant	Intron 10 of 12	1	NM_020726.5	ENSP00000370372.5

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109526 AN: 151998 Hom.: 39823 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.697 AC: 659801 AN: 946720 Hom.: 230887 AF XY: 0.694 AC XY: 330324 AN XY: 475902

African (AFR) AF: 0.809 AC: 17267 AN: 21334

American (AMR) AF: 0.638 AC: 13765 AN: 21576

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 11596 AN: 17180

East Asian (EAS) AF: 0.526 AC: 17978 AN: 34150

South Asian (SAS) AF: 0.659 AC: 36715 AN: 55736

European-Finnish (FIN) AF: 0.766 AC: 29784 AN: 38890

Middle Eastern (MID) AF: 0.629 AC: 2812 AN: 4468

European-Non Finnish (NFE) AF: 0.704 AC: 500329 AN: 711046

Other (OTH) AF: 0.698 AC: 29555 AN: 42340

GnomAD4 genome AF: 0.721 AC: 109617 AN: 152116 Hom.: 39861 Cov.: 32 AF XY: 0.720 AC XY: 53488 AN XY: 74340

African (AFR) AF: 0.802 AC: 33303 AN: 41506

American (AMR) AF: 0.665 AC: 10150 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5162

South Asian (SAS) AF: 0.671 AC: 3236 AN: 4824

European-Finnish (FIN) AF: 0.765 AC: 8101 AN: 10586

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47241 AN: 67986

Other (OTH) AF: 0.692 AC: 1462 AN: 2114

Alfa AF: 0.697 Hom.: 127743

Bravo AF: 0.713

Asia WGS AF: 0.634 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.73
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2561196; hg19: chr5-65105622; COSMIC: COSV66766994;