17-56593839-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

multiple synostoses syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
NOG-related symphalangism spectrum disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
brachydactyly type B2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
multiple synostoses syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
proximal symphalangism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
stapes ankylosis with broad thumbs and toes
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tarsal-carpal coalition syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NOG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2832 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005450.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOG	NM_005450.6	MANE Select	c.-385C>A		5_prime_UTR	Exon 1 of 1	NP_005441.1	Q13253

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOG	ENST00000332822.6	TSL:6 MANE Select	c.-385C>A		5_prime_UTR	Exon 1 of 1	ENSP00000328181.4	Q13253

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

African (AFR)

AF:

0.0408

AC:

AN:

1496

American (AMR)

AF:

0.00387

AC:

AN:

1034

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

AN:

2378

East Asian (EAS)

AF:

0.0232

AC:

AN:

2714

South Asian (SAS)

AF:

0.00489

AC:

AN:

7770

European-Finnish (FIN)

AF:

0.0145

AC:

AN:

4898

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

412

European-Non Finnish (NFE)

AF:

0.00158

AC:

AN:

50486

Other (OTH)

AF:

0.00842

AC:

AN:

4872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0187

AC:

2832

AN:

151810

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.0514

AC:

2128

AN:

41418

American (AMR)

AF:

0.00851

AC:

130

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

AN:

3468

East Asian (EAS)

AF:

0.0493

AC:

251

AN:

5094

South Asian (SAS)

AF:

0.00625

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0150

AC:

158

AN:

10566

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00127

AC:

AN:

67882

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

141

282

424

565

706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000810

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.0250

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.7

(source)

DANN

Benign

0.77

PhyloP100

-0.48

PromoterAI

-0.036

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over