17-77281807-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001113491.2(SEPTIN9):c.19+253C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 494,910 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (3 hom.)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-77281807-C-G is Benign according to our data. Variant chr17-77281807-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00574 (874/152366) while in subpopulation AFR AF= 0.0199 (827/41590). AF 95% confidence interval is 0.0188. There are 7 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 870 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN9	NM_001113491.2	c.19+253C>G		intron_variant		ENST00000427177.6
SEPTIN9-DT	NR_136503.1	n.91G>C		non_coding_transcript_exon_variant	1/3
SEPTIN9	NM_001293695.2	c.19+253C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.19+253C>G		intron_variant		1	NM_001113491.2	A1
SEPTIN9-DT	ENST00000701682.1	n.248G>C		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 870 AN: 152248 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000704 AC: 241 AN: 342544 Hom.: 3 Cov.: 0 AF XY: 0.000637 AC XY: 114 AN XY: 178998

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000674

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00574 AC: 874 AN: 152366 Hom.: 7 Cov.: 33 AF XY: 0.00525 AC XY: 391 AN XY: 74510

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00652

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.6
Dann	Benign	0.65

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: rs183216271; hg19: chr17-75277889;