Variant chr6-32196888-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004557.4(NOTCH4):c.5200+36del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,610,402 control chromosomes in the GnomAD database, including 4,397 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 1051 hom., cov: 31)

Exomes 𝑓: 0.058 ( 3346 hom. )

Consequence

NOTCH4
NM_004557.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.896

Variant links:

Genes affected

NOTCH4 (HGNC:7884): (notch receptor 4) 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 may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

NOTCH4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-32196888-CT-C is Benign according to our data. Variant chr6-32196888-CT-C is described in ClinVar as [Benign]. Clinvar id is 1258765.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NOTCH4	NM_004557.4 linkuse as main transcript	c.5200+36del	intron_variant	ENST00000375023.3	NP_004548.3
NOTCH4	NR_134949.2 linkuse as main transcript	n.4908+36del	intron_variant, non_coding_transcript_variant
NOTCH4	NR_134950.2 linkuse as main transcript	n.4806+36del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NOTCH4	ENST00000375023.3 linkuse as main transcript	c.5200+36del	intron_variant	1	NM_004557.4	ENSP00000364163	P1	Q99466-1
NOTCH4	ENST00000474612.1 linkuse as main transcript	n.3861+36del	intron_variant, non_coding_transcript_variant	5
NOTCH4	ENST00000491215.1 linkuse as main transcript	n.53+36del	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0987

AC:

15006

AN:

152032

Hom.:

1047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0380

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0502

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.0770

AC:

18896

AN:

245332

Hom.:

1036

AF XY:

0.0776

AC XY:

10375

AN XY:

133692

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0595

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0406

Gnomad NFE exome

AF:

0.0525

Gnomad OTH exome

AF:

0.0696

GnomAD4 exome

AF:

0.0581

AC:

84714

AN:

1458252

Hom.:

3346

Cov.:

AF XY:

0.0597

AC XY:

43292

AN XY:

725188

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0622

Gnomad4 ASJ exome

AF:

0.0517

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0418

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0727

GnomAD4 genome

AF:

0.0989

AC:

15049

AN:

152150

Hom.:

1051

Cov.:

AF XY:

0.0988

AC XY:

7349

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0380

Gnomad4 NFE

AF:

0.0502

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0708

Hom.:

109

Bravo

AF:

0.107

Asia WGS

AF:

0.161

AC:

559

AN:

3478

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

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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