Variant 17-56593839-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005450.6(NOG):c.-385C>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 0.0141 in 227,870 control chromosomes in the GnomAD database, including 79 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: 0.0051 ( 6 hom. )

Consequence

NOG
NM_005450.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.481

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-56593839-C-A is Benign according to our data. Variant chr17-56593839-C-A is described in ClinVar as [Benign]. Clinvar id is 1230964.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0187 (2832/151810) while in subpopulation AFR AF= 0.0514 (2128/41418). AF 95% confidence interval is 0.0496. There are 73 homozygotes in gnomad4. There are 1420 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2832 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOG	NM_005450.6 linkuse as main transcript	c.-385C>A		5_prime_UTR_variant	1/1	ENST00000332822.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOG	ENST00000332822.6 linkuse as main transcript	c.-385C>A		5_prime_UTR_variant	1/1		NM_005450.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2816

AN:

151704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0511

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00852

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.0489

Gnomad SAS

AF:

0.00624

Gnomad FIN

AF:

0.0150

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00956

GnomAD4 exome

AF:

0.00514

AC:

391

AN:

76060

Hom.:

Cov.:

AF XY:

0.00548

AC XY:

212

AN XY:

38716

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0232

Gnomad4 SAS exome

AF:

0.00489

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00842

GnomAD4 genome

AF:

0.0187

AC:

2832

AN:

151810

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.00851

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.00625

Gnomad4 FIN

AF:

0.0150

Gnomad4 NFE

AF:

0.00127

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.000810

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.0250

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.88

CADD

Benign

4.7

DANN

Benign

0.77

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