rs2574852

chr17-77495790-A-G

Variant summary

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

The NM_001113491.2(SEPTIN9):c.1574-1525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,094 control chromosomes in the GnomAD database, including 13,954 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 0.42 (13954 hom., cov: 32)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

SEPTIN9 (HGNC:7323): (septin 9) This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.1574-1525A>G		intron_variant		ENST00000427177.6
SEPTIN9	NM_006640.5	c.1520-1525A>G		intron_variant		ENST00000329047.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000329047.13	c.1520-1525A>G		intron_variant		1	NM_006640.5	P3
SEPTIN9	ENST00000427177.6	c.1574-1525A>G		intron_variant		1	NM_001113491.2	A1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63066 AN: 151976 Hom.: 13935 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.415 AC: 63126 AN: 152094 Hom.: 13954 Cov.: 32 AF XY: 0.425 AC XY: 31624 AN XY: 74342

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.426

Alfa AF: 0.401 Hom.: 6903

Bravo AF: 0.423

Asia WGS AF: 0.691 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.017
Dann	Benign	0.45

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: rs2574852; hg19: chr17-75491872;