17-77307420-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001113491.2(SEPTIN9):c.76+223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,294 control chromosomes in the GnomAD database, including 544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (544 hom., cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-77307420-G-A is Benign according to our data. Variant chr17-77307420-G-A is described in ClinVar as [Benign]. Clinvar id is 1296451.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-77307420-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.76+223G>A		intron_variant		ENST00000427177.6
SEPTIN9	NM_001113492.2	c.-417+223G>A		intron_variant
SEPTIN9	NM_001293695.2	c.19+25866G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.76+223G>A		intron_variant		1	NM_001113491.2	A1

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10477 AN: 152176 Hom.: 543 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.00969

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0689 AC: 10499 AN: 152294 Hom.: 544 Cov.: 32 AF XY: 0.0677 AC XY: 5043 AN XY: 74464

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.00969

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.00720 Hom.: 3

Bravo AF: 0.0742

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.25
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs72880527; hg19: chr17-75303502;