5-65761816-A-G

Variant names:

• chr5-65761816-A-G
• rs1301475
• NM_020726.5:c.302-1144A>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.302-1144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,052 control chromosomes in the GnomAD database, including 7,200 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 0.28 (7200 hom., cov: 32)
• Consequence: NLN NM_020726.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLN	NM_020726.5	c.302-1144A>G		intron_variant	Intron 2 of 12	ENST00000380985.10	NP_065777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLN	ENST00000380985.10	c.302-1144A>G		intron_variant	Intron 2 of 12	1	NM_020726.5	ENSP00000370372.5
NLN	ENST00000506539.5	n.418-1144A>G		intron_variant	Intron 2 of 8	1
NLN	ENST00000502464.5	c.-11-1144A>G		intron_variant	Intron 1 of 11	5		ENSP00000423214.1
NLN	ENST00000514991.5	n.*261-1144A>G		intron_variant	Intron 3 of 3	4		ENSP00000422822.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42836 AN: 151934 Hom.: 7189 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.282 AC: 42854 AN: 152052 Hom.: 7200 Cov.: 32 AF XY: 0.288 AC XY: 21420 AN XY: 74296

African (AFR) AF: 0.105 AC: 4346 AN: 41496

American (AMR) AF: 0.428 AC: 6542 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2804 AN: 5176

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3311 AN: 10536

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21995 AN: 67968

Other (OTH) AF: 0.303 AC: 639 AN: 2106

Alfa AF: 0.300 Hom.: 1659

Bravo AF: 0.283

Asia WGS AF: 0.423 AC: 1465 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.60
PhyloP100		0.079
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: rs1301475; hg19: chr5-65057643;