17-77281145-G-T

Variant names:

• chr17-77281145-G-T
• rs7407009
• ENST00000589070.1:c.31+339G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000589070.1(SEPTIN9):​c.31+339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 148,528 control chromosomes in the GnomAD database, including 4,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4107 hom., cov: 31)
• Consequence: SEPTIN9 ENST00000589070.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.101
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-77281145-G-T is Benign according to our data. Variant chr17-77281145-G-T is described in ClinVar as Benign. ClinVar VariationId is 1231914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589070.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9-DT	NR_136503.1		n.286+467C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000589070.1	TSL:3	c.31+339G>T		intron	N/A	ENSP00000465332.1	K7EJV0
	SEPTIN9-DT	ENST00000581153.1	TSL:2	n.286+467C>A		intron	N/A
	SEPTIN9-DT	ENST00000581657.2	TSL:3	n.491+467C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34501 AN: 148420 Hom.: 4106 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.232 AC: 34522 AN: 148528 Hom.: 4107 Cov.: 31 AF XY: 0.229 AC XY: 16548 AN XY: 72400

African (AFR) AF: 0.197 AC: 8096 AN: 41116

American (AMR) AF: 0.238 AC: 3561 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1204 AN: 3402

East Asian (EAS) AF: 0.219 AC: 1113 AN: 5090

South Asian (SAS) AF: 0.167 AC: 803 AN: 4808

European-Finnish (FIN) AF: 0.186 AC: 1770 AN: 9498

Middle Eastern (MID) AF: 0.397 AC: 115 AN: 290

European-Non Finnish (NFE) AF: 0.259 AC: 17186 AN: 66360

Other (OTH) AF: 0.263 AC: 544 AN: 2072

Alfa AF: 0.117 Hom.: 163

Bravo AF: 0.234

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		-0.10
PromoterAI		0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7407009; hg19: chr17-75277227;