rs2561196

chr5-65809795-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	UniProt
NLN	NM_020726.5	c.1714+94G>A		intron_variant		ENST00000380985.10
NLN	XM_005248559.4	c.1660+94G>A		intron_variant
NLN	XM_047417443.1	c.1645+94G>A		intron_variant
NLN	XM_047417444.1	c.1645+94G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLN	ENST00000380985.10	c.1714+94G>A		intron_variant		1	NM_020726.5	P1

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

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.766

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.698

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

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.692

Alfa AF: 0.686 Hom.: 56074

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2561196; hg19: chr5-65105622; COSMIC: COSV66766994;