rs256875

chr5-132767579-G-Achr5-132767579-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098811.2(SEPTIN8):c.31-2050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,838 control chromosomes in the GnomAD database, including 16,240 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 (16240 hom., cov: 31)
• Consequence: SEPTIN8 NM_001098811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN8	NM_001098811.2	c.31-2050C>T		intron_variant		ENST00000378719.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN8	ENST00000378719.7	c.31-2050C>T		intron_variant		1	NM_001098811.2	P3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54088 AN: 151720 Hom.: 16198 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 54201 AN: 151838 Hom.: 16240 Cov.: 31 AF XY: 0.362 AC XY: 26856 AN XY: 74226

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.290

Alfa AF: 0.157 Hom.: 2415

Bravo AF: 0.384

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.036
Dann	Benign	0.56

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: rs256875; hg19: chr5-132103271;