rs2574852

Variant names:

• chr17-77495790-A-G
• rs2574852
• NM_001113491.2:c.1574-1525A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

SEPTIN9 Gene-Disease associations (from GenCC):

• amyotrophic neuralgia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neuralgic amyotrophy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2	c.1574-1525A>G		intron_variant	Intron 10 of 11	ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_006640.5	c.1520-1525A>G		intron_variant	Intron 9 of 10	ENST00000329047.13	NP_006631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.1574-1525A>G		intron_variant	Intron 10 of 11	1	NM_001113491.2	ENSP00000391249.1
SEPTIN9	ENST00000329047.13	c.1520-1525A>G		intron_variant	Intron 9 of 10	1	NM_006640.5	ENSP00000329161.8

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

African (AFR) AF: 0.343 AC: 14238 AN: 41506

American (AMR) AF: 0.567 AC: 8669 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4227 AN: 5150

South Asian (SAS) AF: 0.595 AC: 2874 AN: 4832

European-Finnish (FIN) AF: 0.410 AC: 4332 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26124 AN: 67958

Other (OTH) AF: 0.426 AC: 900 AN: 2114

Alfa AF: 0.398 Hom.: 9216

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
PhyloP100		-2.1
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: rs2574852; hg19: chr17-75491872;