rs30527

Positions:

• chr5-132774050-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SEPTIN8	NM_001098811.2	c.30+3058C>T		intron_variant		ENST00000378719.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN8	ENST00000378719.7	c.30+3058C>T		intron_variant		1	NM_001098811.2	P3

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.308

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

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.291

Alfa AF: 0.173 Hom.: 4156

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

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

LitVar

Other links and lift over

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