Variant chr17-77281386-G-T 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 ENST00000589070.1(SEPTIN9):c.31+580G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 702,090 control chromosomes in the GnomAD database, including 723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 121 hom., cov: 31)

Exomes 𝑓: 0.043 ( 602 hom. )

Consequence

SEPTIN9
ENST00000589070.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.136

Variant links:

Genes affected

SEPTIN9 (HGNC:7323): (septin 9) This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]

SEPTIN9 links:

SEPTIN9-DT (HGNC:52818): (SEPTIN9 divergent transcript)

SEPTIN9-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-77281386-G-T is Benign according to our data. Variant chr17-77281386-G-T is described in ClinVar as [Benign]. Clinvar id is 1227821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9-DT	NR_136503.1 link	n.286+226C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
SEPTIN9	ENST00000589070.1 link	c.31+580G>T	intron_variant	3	ENSP00000465332.1	K7EJV0
SEPTIN9-DT	ENST00000581153.1 link	n.286+226C>A	intron_variant	2
SEPTIN9-DT	ENST00000701682.1 link	n.443+226C>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0356

AC:

5027

AN:

141144

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00942

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000212

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.0354

Gnomad MID

AF:

0.0171

Gnomad NFE

AF:

0.0557

Gnomad OTH

AF:

0.0365

GnomAD4 exome

AF:

0.0434

AC:

24363

AN:

560866

Hom.:

602

Cov.:

AF XY:

0.0435

AC XY:

12677

AN XY:

291540

show subpopulations

Gnomad4 AFR exome

AF:

0.00798

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.0000793

Gnomad4 SAS exome

AF:

0.0325

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.0506

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0356

AC:

5024

AN:

141224

Hom.:

121

Cov.:

AF XY:

0.0332

AC XY:

2272

AN XY:

68470

show subpopulations

Gnomad4 AFR

AF:

0.00940

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000212

Gnomad4 SAS

AF:

0.0287

Gnomad4 FIN

AF:

0.0354

Gnomad4 NFE

AF:

0.0557

Gnomad4 OTH

AF:

0.0362

Alfa

AF:

0.0178

Hom.:

Asia WGS

AF:

0.0100

AC:

AN:

3406

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	clinical testing	GeneDx	Aug 06, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

DANN

Benign

0.85

Splicing

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