Variant 19-5824309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004558.5(NRTN):c.144C>T(p.Asp48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,606,660 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 137 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 110 hom. )

Consequence

NRTN
NM_004558.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.179

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 -13 ACMG points.

BP4

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

BP6

Variant 19-5824309-C-T is Benign according to our data. Variant chr19-5824309-C-T is described in ClinVar as [Benign]. Clinvar id is 259425.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.179 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRTN	NM_004558.5 linkuse as main transcript	c.144C>T	p.Asp48=	synonymous_variant	2/3	ENST00000303212.3
NRTN	XM_047438890.1 linkuse as main transcript	c.144C>T	p.Asp48=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRTN	ENST00000303212.3 linkuse as main transcript	c.144C>T	p.Asp48=	synonymous_variant	2/3	1	NM_004558.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3502

AN:

152184

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00597

AC:

1393

AN:

233450

Hom.:

AF XY:

0.00454

AC XY:

578

AN XY:

127206

show subpopulations

Gnomad AFR exome

AF:

0.0844

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000763

Gnomad OTH exome

AF:

0.00174

GnomAD4 exome

AF:

0.00218

AC:

3166

AN:

1454358

Hom.:

110

Cov.:

AF XY:

0.00182

AC XY:

1316

AN XY:

723262

show subpopulations

Gnomad4 AFR exome

AF:

0.0775

Gnomad4 AMR exome

AF:

0.00390

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000892

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.0230

AC:

3504

AN:

152302

Hom.:

137

Cov.:

AF XY:

0.0222

AC XY:

1653

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0801

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00433

AC:

AN:

3478

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 submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.3

DANN

Benign

0.82

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