rs758377

Positions:

• chr17-58529763-T-C
• chr17-58529763-T-G

Variant summary

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

The NM_001368771.2(SEPTIN4):​c.1615-2785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,548 control chromosomes in the GnomAD database, including 53,813 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 0.84 (53794 hom., cov: 29)
  • Exomes 𝑓: 0.77 (19 hom.)
• Consequence: SEPTIN4 NM_001368771.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

SEPTIN4 (HGNC:9165): (septin 4) 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. This gene is highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]

SEPTIN4 (HGNC:):

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 = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN4	NM_001368771.2	c.1615-2785A>G		intron_variant		ENST00000672673.2	NP_001355700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN4	ENST00000672673.2	c.1615-2785A>G		intron_variant			NM_001368771.2	ENSP00000500383.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127249 AN: 151374 Hom.: 53730 Cov.: 29

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.767 AC: 46 AN: 60 Hom.: 19 AF XY: 0.737 AC XY: 28 AN XY: 38

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.841 AC: 127372 AN: 151488 Hom.: 53794 Cov.: 29 AF XY: 0.844 AC XY: 62411 AN XY: 73930

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.810

Alfa AF: 0.797 Hom.: 8621

Bravo AF: 0.844

Asia WGS AF: 0.955 AC: 3321 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	0.22
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: rs758377; hg19: chr17-56607124;