Genetic Variant NLN:c.1714+94G>A (chr5-65809795-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

7 publications found

Variant links:

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]

NLN links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020726.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLN	NM_020726.5	MANE Select	c.1714+94G>A		intron	N/A	NP_065777.1	Q9BYT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLN	ENST00000380985.10	TSL:1 MANE Select	c.1714+94G>A	intron	N/A	ENSP00000370372.5	Q9BYT8
NLN	ENST00000865845.1		c.1714+94G>A	intron	N/A	ENSP00000535904.1
NLN	ENST00000865846.1		c.1606+94G>A	intron	N/A	ENSP00000535905.1

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109526

AN:

151998

Hom.:

39823

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10091

20182

30273

40364

50455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11242

22484

33726

44968

56210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.721

AC:

109617

AN:

152116

Hom.:

39861

Cov.:

AF XY:

0.720

AC XY:

53488

AN XY:

74340

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1555

3110

4665

6220

7775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.026

(source)

DANN

Benign

0.73

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over