rs103550

Positions:

• chr17-77384092-G-C
• chr17-77384092-G-T

Variant summary

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

The ENST00000427177.6(SEPTIN9):​c.77-17967G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,088 control chromosomes in the GnomAD database, including 35,284 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 0.68 (35284 hom., cov: 32)
• Consequence: SEPTIN9 ENST00000427177.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN9	NM_001113491.2	c.77-17967G>C		intron_variant		ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_006640.5	c.23-17967G>C		intron_variant		ENST00000329047.13	NP_006631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000329047.13	c.23-17967G>C		intron_variant		1	NM_006640.5	ENSP00000329161	P3
SEPTIN9	ENST00000427177.6	c.77-17967G>C		intron_variant		1	NM_001113491.2	ENSP00000391249	A1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103364 AN: 151970 Hom.: 35240 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.680 AC: 103459 AN: 152088 Hom.: 35284 Cov.: 32 AF XY: 0.677 AC XY: 50354 AN XY: 74336

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.689

Alfa AF: 0.674 Hom.: 4309

Bravo AF: 0.684

Asia WGS AF: 0.683 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.067
DANN	Benign	0.67

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: rs103550; hg19: chr17-75380174;