17-77281348-C-G

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+264G>C 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 0.147 in 540,976 control chromosomes in the GnomAD database, including 6,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1487 hom., cov: 26)
  • Exomes 𝑓: 0.15 (5002 hom.)
• Consequence: SEPTIN9-DT NR_136503.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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=-0.82).
• BP6: Variant 17-77281348-C-G is Benign according to our data. Variant chr17-77281348-C-G is described in ClinVar as [Benign]. Clinvar id is 1248488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9-DT	NR_136503.1	n.286+264G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9-DT	ENST00000701682.1	n.443+264G>C		intron_variant, non_coding_transcript_variant
SEPTIN9	ENST00000589070.1	c.31+542C>G		intron_variant		3
SEPTIN9-DT	ENST00000581153.1	n.286+264G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 20032 AN: 136014 Hom.: 1487 Cov.: 26

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.147 AC: 59536 AN: 404884 Hom.: 5002 AF XY: 0.145 AC XY: 30959 AN XY: 213658

Gnomad4 AFR exome AF: 0.0942

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.00449

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.147 AC: 20041 AN: 136092 Hom.: 1487 Cov.: 26 AF XY: 0.147 AC XY: 9572 AN XY: 65216

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.163

Alfa AF: 0.0565 Hom.: 46

Bravo AF: 0.135

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.6
Dann	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4789430; hg19: chr17-75277430;