5-132757957-T-C

Variant names:

• chr5-132757957-T-C
• rs30534
• ENST00000296873.11:c.*864A>G

Variant summary

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

The ENST00000296873.11(SEPTIN8):​c.*864A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 985,860 control chromosomes in the GnomAD database, including 29,913 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 (16987 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12926 hom.)
• Consequence: SEPTIN8 ENST00000296873.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296873.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN8	NM_001098811.2	MANE Select	c.1286+2845A>G		intron	N/A	NP_001092281.1
	SEPTIN8	NM_001098812.2		c.*557A>G		3_prime_UTR	Exon 10 of 10	NP_001092282.1
	SEPTIN8	NM_001300798.2		c.*557A>G		3_prime_UTR	Exon 10 of 10	NP_001287727.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN8	ENST00000296873.11	TSL:1	c.*864A>G		3_prime_UTR	Exon 10 of 10	ENSP00000296873.7
	SEPTIN8	ENST00000448933.5	TSL:1	c.*864A>G		3_prime_UTR	Exon 10 of 10	ENSP00000399840.1
	SEPTIN8	ENST00000378719.7	TSL:1 MANE Select	c.1286+2845A>G		intron	N/A	ENSP00000367991.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55300 AN: 151972 Hom.: 16940 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.136 AC: 113239 AN: 833770 Hom.: 12926 Cov.: 32 AF XY: 0.133 AC XY: 51285 AN XY: 385036

African (AFR) AF: 0.857 AC: 13532 AN: 15788

American (AMR) AF: 0.325 AC: 348 AN: 1072

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 699 AN: 5154

East Asian (EAS) AF: 0.733 AC: 2665 AN: 3638

South Asian (SAS) AF: 0.134 AC: 2208 AN: 16498

European-Finnish (FIN) AF: 0.275 AC: 77 AN: 280

Middle Eastern (MID) AF: 0.167 AC: 271 AN: 1620

European-Non Finnish (NFE) AF: 0.116 AC: 88288 AN: 762406

Other (OTH) AF: 0.189 AC: 5151 AN: 27314

GnomAD4 genome AF: 0.364 AC: 55417 AN: 152090 Hom.: 16987 Cov.: 32 AF XY: 0.369 AC XY: 27428 AN XY: 74340

African (AFR) AF: 0.807 AC: 33450 AN: 41452

American (AMR) AF: 0.300 AC: 4583 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3793 AN: 5170

South Asian (SAS) AF: 0.168 AC: 809 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3080 AN: 10578

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8508 AN: 68006

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.201 Hom.: 7354

Bravo AF: 0.392

Asia WGS AF: 0.431 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs30534; hg19: chr5-132093649;