rs30527

Variant names:

• chr5-132774050-G-A
• rs30527
• NM_001098811.2:c.30+3058C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098811.2(SEPTIN8):​c.30+3058C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 158,716 control chromosomes in the GnomAD database, including 16,587 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 0.36 (16329 hom., cov: 32)
  • Exomes 𝑓: 0.28 (258 hom.)
• Consequence: SEPTIN8 NM_001098811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 12 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN8	NM_001098811.2	c.30+3058C>T		intron_variant	Intron 1 of 9	ENST00000378719.7	NP_001092281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN8	ENST00000378719.7	c.30+3058C>T		intron_variant	Intron 1 of 9	1	NM_001098811.2	ENSP00000367991.2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54287 AN: 151976 Hom.: 16287 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.276 AC: 1830 AN: 6622 Hom.: 258 Cov.: 0 AF XY: 0.280 AC XY: 903 AN XY: 3220

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.277 AC: 1805 AN: 6516

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 8 AN: 48

Other (OTH) AF: 0.308 AC: 16 AN: 52

GnomAD4 genome AF: 0.358 AC: 54398 AN: 152094 Hom.: 16329 Cov.: 32 AF XY: 0.363 AC XY: 26961 AN XY: 74346

African (AFR) AF: 0.787 AC: 32666 AN: 41500

American (AMR) AF: 0.293 AC: 4480 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3826 AN: 5154

South Asian (SAS) AF: 0.165 AC: 794 AN: 4820

European-Finnish (FIN) AF: 0.291 AC: 3075 AN: 10572

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8391 AN: 67976

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.200 Hom.: 7390

Bravo AF: 0.384

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.69
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs30527; hg19: chr5-132109742; COSMIC: COSV51524491;