17-77281145-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_136503.1(SEPTIN9-DT):n.286+467C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 148,528 control chromosomes in the GnomAD database, including 4,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4107 hom., cov: 31)
• Consequence: SEPTIN9-DT NR_136503.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.101

Genes affected

SEPTIN9-DT (HGNC:52818): (SEPTIN9 divergent transcript)

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-77281145-G-T is Benign according to our data. Variant chr17-77281145-G-T is described in ClinVar as [Benign]. Clinvar id is 1231914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9-DT	NR_136503.1	n.286+467C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9-DT	ENST00000701682.1	n.443+467C>A		intron_variant, non_coding_transcript_variant
SEPTIN9	ENST00000589070.1	c.31+339G>T		intron_variant		3
SEPTIN9-DT	ENST00000581153.1	n.286+467C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34501 AN: 148420 Hom.: 4106 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.232 AC: 34522 AN: 148528 Hom.: 4107 Cov.: 31 AF XY: 0.229 AC XY: 16548 AN XY: 72400

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.263

Alfa AF: 0.117 Hom.: 163

Bravo AF: 0.234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.3
Dann	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7407009; hg19: chr17-75277227;