Variant chr17-77281351-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000589070.1(SEPTIN9):c.31+545T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 536,186 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 101 hom., cov: 27)

Exomes 𝑓: 0.037 ( 341 hom. )

Consequence

SEPTIN9
ENST00000589070.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.459

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:

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=-0.8).

BP6

Variant 17-77281351-T-G is Benign according to our data. Variant chr17-77281351-T-G is described in ClinVar as [Benign]. Clinvar id is 1255034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0349 (4429/126886) while in subpopulation NFE AF= 0.0477 (2921/61218). AF 95% confidence interval is 0.0463. There are 101 homozygotes in gnomad4. There are 2156 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4429 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9-DT	NR_136503.1 link	n.286+261A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
SEPTIN9	ENST00000589070.1 link	c.31+545T>G	intron_variant	3	ENSP00000465332.1	K7EJV0
SEPTIN9-DT	ENST00000581153.1 link	n.286+261A>C	intron_variant	2
SEPTIN9-DT	ENST00000701682.1 link	n.443+261A>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

4432

AN:

126854

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00988

Gnomad AMR

AF:

0.0267

Gnomad ASJ

AF:

0.0198

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.0144

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0217

GnomAD4 exome

AF:

0.0373

AC:

15263

AN:

409300

Hom.:

341

AF XY:

0.0365

AC XY:

7886

AN XY:

216026

show subpopulations

Gnomad4 AFR exome

AF:

0.00679

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0173

Gnomad4 FIN exome

AF:

0.0645

Gnomad4 NFE exome

AF:

0.0443

Gnomad4 OTH exome

AF:

0.0326

GnomAD4 genome

AF:

0.0349

AC:

4429

AN:

126886

Hom.:

101

Cov.:

AF XY:

0.0358

AC XY:

2156

AN XY:

60216

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0266

Gnomad4 ASJ

AF:

0.0198

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0183

Gnomad4 FIN

AF:

0.0947

Gnomad4 NFE

AF:

0.0477

Gnomad4 OTH

AF:

0.0216

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0256

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	Jul 21, 2018	- -
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

-0.80

CADD

Benign

4.3

DANN

Benign

0.19

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