10-70432196-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018055.5(NODAL):c.*740T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,928 control chromosomes in the GnomAD database, including 17,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16972 hom., cov: 34)

Exomes 𝑓: 0.49 ( 99 hom. )

Consequence

NODAL
NM_018055.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

NODAL (HGNC:7865): (nodal growth differentiation factor) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which regulates early embryonic development. This protein is required for maintenance of human embryonic stem cell pluripotency and may play a role in human placental development. Mutations in this gene are associated with heterotaxy, a condition characterized by random orientation of visceral organs with respect to the left-right axis. [provided by RefSeq, Aug 2016]

NODAL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 10-70432196-A-G is Benign according to our data. Variant chr10-70432196-A-G is described in ClinVar as [Benign]. Clinvar id is 300288.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-70432196-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NODAL	NM_018055.5 linkuse as main transcript	c.*740T>C	3_prime_UTR_variant	3/3	ENST00000287139.8
NODAL	NM_001329906.2 linkuse as main transcript	c.*740T>C	3_prime_UTR_variant	3/3
NODAL	XM_024448028.2 linkuse as main transcript	c.*740T>C	3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NODAL	ENST00000287139.8 linkuse as main transcript	c.*740T>C		3_prime_UTR_variant	3/3	1	NM_018055.5	P1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70400

AN:

151994

Hom.:

16960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.721

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.493

AC:

402

AN:

816

Hom.:

AF XY:

0.489

AC XY:

215

AN XY:

440

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.463

AC:

70435

AN:

152112

Hom.:

16972

Cov.:

AF XY:

0.467

AC XY:

34732

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.356

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.721

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.481

Alfa

AF:

0.490

Hom.:

31628

Bravo

AF:

0.454

Asia WGS

AF:

0.598

AC:

2078

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Holoprosencephaly sequence

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Heterotaxy, visceral, 5, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.49

Splicing

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