Variant 17-56594151-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005450.6(NOG):c.-73G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,338,074 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 73 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 83 hom. )

Consequence

NOG
NM_005450.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.413

Variant links:

Genes affected

NOG (HGNC:7866): (noggin) The secreted polypeptide, encoded by this gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, this protein may have a principal role in creating morphogenic gradients. The protein appears to have pleiotropic effect, both early in development as well as in later stages. It was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of the ortholog suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. Recently, several dominant human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) were identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region (17q22) as this gene. All of these mutations altered evolutionarily conserved amino acid residues. The amino acid sequence of this human gene is highly homologous to that of Xenopus, rat and mouse. [provided by RefSeq, Jul 2008]

NOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-56594151-G-A is Benign according to our data. Variant chr17-56594151-G-A is described in ClinVar as [Benign]. Clinvar id is 1258795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOG	NM_005450.6 linkuse as main transcript	c.-73G>A		5_prime_UTR_variant	1/1	ENST00000332822.6	NP_005441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOG	ENST00000332822.6 linkuse as main transcript	c.-73G>A		5_prime_UTR_variant	1/1		NM_005450.6	ENSP00000328181	P1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2821

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.0485

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0150

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00956

GnomAD4 exome

AF:

0.00404

AC:

4790

AN:

1185888

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

2342

AN XY:

588888

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

Gnomad4 AMR exome

AF:

0.00683

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.0312

Gnomad4 SAS exome

AF:

0.00410

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.000903

Gnomad4 OTH exome

AF:

0.00982

GnomAD4 genome

AF:

0.0186

AC:

2837

AN:

152186

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1429

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0512

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.0489

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.0150

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.0199

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

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