dbSNP rs256871: SEPTIN8:c.*1476C>T (chr5-132757345-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000296873.11(SEPTIN8):c.*1476C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 985,116 control chromosomes in the GnomAD database, including 12,807 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 0.23 ( 5311 hom., cov: 32)

Exomes 𝑓: 0.12 ( 7496 hom. )

Consequence

SEPTIN8
ENST00000296873.11 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

12 publications found

Variant links:

Genes affected

SEPTIN8 (HGNC:16511): (septin 8) 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

SEPTIN8 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 = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN8	NM_001098811.2 link	c.1286+3457C>T		intron_variant	Intron 9 of 9	ENST00000378719.7	NP_001092281.1	Q92599-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN8	ENST00000378719.7 link	c.1286+3457C>T		intron_variant	Intron 9 of 9	1	NM_001098811.2	ENSP00000367991.2		Q92599-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34320

AN:

151856

Hom.:

5312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.122

AC:

101996

AN:

833142

Hom.:

7496

Cov.:

AF XY:

0.120

AC XY:

46359

AN XY:

384734

show subpopulations

African (AFR)

AF:

0.344

AC:

5437

AN:

15788

American (AMR)

AF:

0.299

AC:

294

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

669

AN:

5152

East Asian (EAS)

AF:

0.732

AC:

2656

AN:

3630

South Asian (SAS)

AF:

0.132

AC:

2179

AN:

16458

European-Finnish (FIN)

AF:

0.283

AC:

AN:

286

Middle Eastern (MID)

AF:

0.120

AC:

195

AN:

1622

European-Non Finnish (NFE)

AF:

0.113

AC:

86059

AN:

761922

Other (OTH)

AF:

0.162

AC:

4426

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5386

10772

16157

21543

26929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4450

8900

13350

17800

22250

<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:

0.226

AC:

34360

AN:

151974

Hom.:

5311

Cov.:

AF XY:

0.235

AC XY:

17422

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.334

AC:

13851

AN:

41458

American (AMR)

AF:

0.239

AC:

3651

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

473

AN:

3472

East Asian (EAS)

AF:

0.734

AC:

3783

AN:

5154

South Asian (SAS)

AF:

0.165

AC:

793

AN:

4802

European-Finnish (FIN)

AF:

0.291

AC:

3065

AN:

10534

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8269

AN:

67958

Other (OTH)

AF:

0.200

AC:

422

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1224

2448

3672

4896

6120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.160

Hom.:

4790

Bravo

AF:

0.232

Asia WGS

AF:

0.401

AC:

1394

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

0.097

(source)

DANN

Benign

0.68

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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