rs256871

chr5-132757345-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.9).
• 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/exons	MANE	UniProt
SEPTIN8	NM_001098811.2	c.1286+3457C>T		intron_variant		ENST00000378719.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN8	ENST00000378719.7	c.1286+3457C>T		intron_variant		1	NM_001098811.2	P3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34320 AN: 151856 Hom.: 5312 Cov.: 32

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.: 31 AF XY: 0.120 AC XY: 46359 AN XY: 384734

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.226 AC: 34360 AN: 151974 Hom.: 5311 Cov.: 32 AF XY: 0.235 AC XY: 17422 AN XY: 74242

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.200

Alfa AF: 0.141 Hom.: 2044

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
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs256871; hg19: chr5-132093037;