Genetic Variant SEPTIN9:c.31+580G>T (chr17-77281386-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEPTIN9-DT	NR_136503.1		n.286+226C>A	intron	N/A
SEPTIN9	NM_001113491.2	MANE Select	c.-150G>T	upstream_gene	N/A	NP_001106963.1	Q9UHD8-1
SEPTIN9	NM_001293695.2		c.-150G>T	upstream_gene	N/A	NP_001280624.1	Q9UHD8-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEPTIN9	ENST00000589070.1	TSL:3	c.31+580G>T	intron	N/A	ENSP00000465332.1	K7EJV0
SEPTIN9-DT	ENST00000581153.1	TSL:2	n.286+226C>A	intron	N/A
SEPTIN9-DT	ENST00000581657.2	TSL:3	n.491+226C>A	intron	N/A

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

African (AFR)

AF:

0.00798

AC:

AN:

11408

American (AMR)

AF:

0.0168

AC:

341

AN:

20278

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

658

AN:

14714

East Asian (EAS)

AF:

0.0000793

AC:

AN:

25208

South Asian (SAS)

AF:

0.0325

AC:

1547

AN:

47562

European-Finnish (FIN)

AF:

0.0406

AC:

1207

AN:

29714

Middle Eastern (MID)

AF:

0.0297

AC:

AN:

2256

European-Non Finnish (NFE)

AF:

0.0506

AC:

19268

AN:

380588

Other (OTH)

AF:

0.0406

AC:

1182

AN:

29138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1120

2239

3359

4478

5598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0356

AC:

5024

AN:

141224

Hom.:

121

Cov.:

AF XY:

0.0332

AC XY:

2272

AN XY:

68470

show subpopulations

African (AFR)

AF:

0.00940

AC:

366

AN:

38920

American (AMR)

AF:

0.0259

AC:

377

AN:

14554

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

160

AN:

3266

East Asian (EAS)

AF:

0.000212

AC:

AN:

4712

South Asian (SAS)

AF:

0.0287

AC:

127

AN:

4424

European-Finnish (FIN)

AF:

0.0354

AC:

314

AN:

8872

Middle Eastern (MID)

AF:

0.0147

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0557

AC:

3534

AN:

63394

Other (OTH)

AF:

0.0362

AC:

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

216

431

647

862

1078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0178

Hom.:

Asia WGS

AF:

0.0100

AC:

AN:

3406

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

(source)

DANN

Benign

0.85

PhyloP100

-0.14

PromoterAI

-0.0015

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over