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GeneBe

rs7255720

chr19-5828053-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_004558.5(NRTN):c.474G>C(p.Arg158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,427,226 control chromosomes in the GnomAD database, including 2,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.071 ( 520 hom., cov: 32)
Exomes 𝑓: 0.049 ( 2015 hom. )

Consequence

NRTN
NM_004558.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.601
Variant links:
Genes affected
NRTN (HGNC:8007): (neurturin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. A neurturin mutation has been described in a family with Hirschsprung Disease. [provided by RefSeq, Aug 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-5828053-G-C is Benign according to our data. Variant chr19-5828053-G-C is described in ClinVar as [Benign]. Clinvar id is 259428.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.601 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NRTNNM_004558.5 linkuse as main transcriptc.474G>C p.Arg158= synonymous_variant 3/3 ENST00000303212.3
NRTNXM_047438890.1 linkuse as main transcriptc.474G>C p.Arg158= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRTNENST00000303212.3 linkuse as main transcriptc.474G>C p.Arg158= synonymous_variant 3/31 NM_004558.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0707
AC:
10658
AN:
150716
Hom.:
520
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.130
Gnomad AMI
AF:
0.0208
Gnomad AMR
AF:
0.0480
Gnomad ASJ
AF:
0.0665
Gnomad EAS
AF:
0.103
Gnomad SAS
AF:
0.130
Gnomad FIN
AF:
0.0291
Gnomad MID
AF:
0.0350
Gnomad NFE
AF:
0.0397
Gnomad OTH
AF:
0.0741
GnomAD3 exomes
AF:
0.0503
AC:
2492
AN:
49592
Hom.:
88
AF XY:
0.0570
AC XY:
1673
AN XY:
29328
show subpopulations
Gnomad AFR exome
AF:
0.103
Gnomad AMR exome
AF:
0.0257
Gnomad ASJ exome
AF:
0.0530
Gnomad EAS exome
AF:
0.0723
Gnomad SAS exome
AF:
0.107
Gnomad FIN exome
AF:
0.0200
Gnomad NFE exome
AF:
0.0347
Gnomad OTH exome
AF:
0.0478
GnomAD4 exome
AF:
0.0494
AC:
63114
AN:
1276404
Hom.:
2015
Cov.:
33
AF XY:
0.0513
AC XY:
32187
AN XY:
627342
show subpopulations
Gnomad4 AFR exome
AF:
0.129
Gnomad4 AMR exome
AF:
0.0340
Gnomad4 ASJ exome
AF:
0.0652
Gnomad4 EAS exome
AF:
0.0728
Gnomad4 SAS exome
AF:
0.128
Gnomad4 FIN exome
AF:
0.0290
Gnomad4 NFE exome
AF:
0.0420
Gnomad4 OTH exome
AF:
0.0606
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0708
AC:
10685
AN:
150822
Hom.:
520
Cov.:
32
AF XY:
0.0715
AC XY:
5260
AN XY:
73596
show subpopulations
Gnomad4 AFR
AF:
0.131
Gnomad4 AMR
AF:
0.0480
Gnomad4 ASJ
AF:
0.0665
Gnomad4 EAS
AF:
0.103
Gnomad4 SAS
AF:
0.131
Gnomad4 FIN
AF:
0.0291
Gnomad4 NFE
AF:
0.0397
Gnomad4 OTH
AF:
0.0776
Alfa
AF:
0.0536
Hom.:
45
Bravo
AF:
0.0722
Asia WGS
AF:
0.154
AC:
523
AN:
3394

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
11
Dann
Benign
0.89

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7255720; hg19: chr19-5828064; API