Variant 9-136494732-A-G 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_017617.5(NOTCH1):c.*1339T>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 0.513 in 398,470 control chromosomes in the GnomAD database, including 53,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20055 hom., cov: 34)

Exomes 𝑓: 0.52 ( 33922 hom. )

Consequence

NOTCH1
NM_017617.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.585

Variant links:

Genes affected

NOTCH1 (HGNC:7881): (notch receptor 1) This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor plays a role in the development of numerous cell and tissue types. Mutations in this gene are associated with aortic valve disease, Adams-Oliver syndrome, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and head and neck squamous cell carcinoma. [provided by RefSeq, Jan 2016]

NOTCH1 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=-0.91).

BP6

Variant 9-136494732-A-G is Benign according to our data. Variant chr9-136494732-A-G is described in ClinVar as [Benign]. Clinvar id is 1288748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOTCH1	NM_017617.5 link	c.*1339T>C		3_prime_UTR_variant	Exon 34 of 34	ENST00000651671.1	NP_060087.3	P46531
NOTCH1	XM_011518717.3 link	c.*1339T>C		3_prime_UTR_variant	Exon 31 of 31		XP_011517019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOTCH1	ENST00000651671 link	c.*1339T>C		3_prime_UTR_variant	Exon 34 of 34		NM_017617.5	ENSP00000498587.1		P46531

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77297

AN:

151992

Hom.:

20015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.498

GnomAD4 exome

AF:

0.516

AC:

127093

AN:

246360

Hom.:

33922

Cov.:

AF XY:

0.511

AC XY:

63851

AN XY:

124850

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.773

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.557

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.496

GnomAD4 genome

AF:

0.509

AC:

77378

AN:

152110

Hom.:

20055

Cov.:

AF XY:

0.508

AC XY:

37793

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.724

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.563

Gnomad4 NFE

AF:

0.485

Gnomad4 OTH

AF:

0.498

Alfa

AF:

0.482

Hom.:

16702

Bravo

AF:

0.509

Asia WGS

AF:

0.458

AC:

1594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30629480) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.23

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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