5-132770869-A-T

Variant names:

• chr5-132770869-A-T
• rs392916
• NM_001098811.2:c.31-5340T>A

Variant summary

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

The NM_001098811.2(SEPTIN8):​c.31-5340T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,246 control chromosomes in the GnomAD database, including 2,375 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 0.13 (2375 hom., cov: 31)
• Consequence: SEPTIN8 NM_001098811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098811.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN8	NM_001098811.2	MANE Select	c.31-5340T>A		intron	N/A	NP_001092281.1	Q92599-1
	SEPTIN8	NM_001098812.2		c.31-5340T>A		intron	N/A	NP_001092282.1	Q92599-4
	SEPTIN8	NM_001300798.2		c.31-5340T>A		intron	N/A	NP_001287727.1	A6NFQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN8	ENST00000378719.7	TSL:1 MANE Select	c.31-5340T>A		intron	N/A	ENSP00000367991.2	Q92599-1
	SEPTIN8	ENST00000296873.11	TSL:1	c.31-5340T>A		intron	N/A	ENSP00000296873.7	Q92599-2
	SEPTIN8	ENST00000448933.5	TSL:1	c.-150-5340T>A		intron	N/A	ENSP00000399840.1	Q92599-3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20304 AN: 152128 Hom.: 2376 Cov.: 31

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.133 AC: 20323 AN: 152246 Hom.: 2375 Cov.: 31 AF XY: 0.145 AC XY: 10786 AN XY: 74446

African (AFR) AF: 0.0586 AC: 2436 AN: 41546

American (AMR) AF: 0.174 AC: 2668 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3352 AN: 5174

South Asian (SAS) AF: 0.152 AC: 736 AN: 4832

European-Finnish (FIN) AF: 0.278 AC: 2943 AN: 10590

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7603 AN: 68012

Other (OTH) AF: 0.121 AC: 255 AN: 2116

Alfa AF: 0.0616 Hom.: 76

Bravo AF: 0.126

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.75
PhyloP100		-0.75
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs392916;

hg19: chr5-132106561;