Variant rs7255720 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000303212.3(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
ENST00000303212.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NRTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.601 with no splicing effect.

BA1

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	Protein	UniProt
NRTN	NM_004558.5 linkuse as main transcript	c.474G>C	p.Arg158=	synonymous_variant	3/3	ENST00000303212.3	NP_004549.1
NRTN	XM_047438890.1 linkuse as main transcript	c.474G>C	p.Arg158=	synonymous_variant	2/2		XP_047294846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRTN	ENST00000303212.3 linkuse as main transcript	c.474G>C	p.Arg158=	synonymous_variant	3/3	1	NM_004558.5	ENSP00000302648	P1

Frequencies

GnomAD3 genomes

AF:

0.0707

AC:

10658

AN:

150716

Hom.:

520

Cov.:

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.:

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.:

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

AF:

0.0708

AC:

10685

AN:

150822

Hom.:

520

Cov.:

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.:

Bravo

AF:

0.0722

Asia WGS

AF:

0.154

AC:

523

AN:

3394

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over