dbSNP rs758377: SEPTIN4:c.1615-2785A>G (chr17-58529763-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001368771.2(SEPTIN4):c.1615-2785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,548 control chromosomes in the GnomAD database, including 53,813 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 53794 hom., cov: 29)

Exomes 𝑓: 0.77 ( 19 hom. )

Consequence

SEPTIN4
NM_001368771.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

5 publications found

Variant links:

Genes affected

SEPTIN4 (HGNC:9165): (septin 4) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]

SEPTIN4 links:

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

SEPTIN4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN4	NM_001368771.2 link	c.1615-2785A>G		intron_variant	Intron 3 of 13	ENST00000672673.2	NP_001355700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN4	ENST00000672673.2 link	c.1615-2785A>G		intron_variant	Intron 3 of 13		NM_001368771.2	ENSP00000500383.1		O43236-7

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127249

AN:

151374

Hom.:

53730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

0.821

Gnomad AMR

AF:

0.847

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.808

GnomAD4 exome

AF:

0.767

AC:

AN:

Hom.:

AF XY:

0.737

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.760

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.581

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.841

AC:

127372

AN:

151488

Hom.:

53794

Cov.:

AF XY:

0.844

AC XY:

62411

AN XY:

73930

show subpopulations

African (AFR)

AF:

0.909

AC:

37493

AN:

41226

American (AMR)

AF:

0.847

AC:

12924

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

2704

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5154

AN:

5164

South Asian (SAS)

AF:

0.900

AC:

4327

AN:

4810

European-Finnish (FIN)

AF:

0.831

AC:

8574

AN:

10320

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.788

AC:

53512

AN:

67928

Other (OTH)

AF:

0.810

AC:

1706

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1033

2066

3100

4133

5166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.798

Hom.:

18360

Bravo

AF:

0.844

Asia WGS

AF:

0.955

AC:

3321

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.22

(source)

DANN

Benign

0.56

PhyloP100

-1.7

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over