17-77281348-C-A

Variant names:

• chr17-77281348-C-A
• rs4789430
• ENST00000589070.1:c.31+542C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000589070.1(SEPTIN9):​c.31+542C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 541,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: SEPTIN9 ENST00000589070.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN9-DT	NR_136503.1	n.286+264G>T		intron_variant	Intron 1 of 2
SEPTIN9	NM_001113491.2	c.-188C>A		upstream_gene_variant		ENST00000427177.6	NP_001106963.1
SEPTIN9	NM_001293695.2	c.-188C>A		upstream_gene_variant			NP_001280624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN9	ENST00000427177.6	c.-188C>A		upstream_gene_variant		1	NM_001113491.2	ENSP00000391249.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 17 AN: 136078 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000237

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: 0.000156

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 42 AN: 405214 Hom.: 0 AF XY: 0.0000982 AC XY: 21 AN XY: 213818

African (AFR) AF: 0.00 AC: 0 AN: 8164

American (AMR) AF: 0.000245 AC: 3 AN: 12240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12134

East Asian (EAS) AF: 0.00 AC: 0 AN: 23628

South Asian (SAS) AF: 0.00 AC: 0 AN: 39914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1838

European-Non Finnish (NFE) AF: 0.000149 AC: 38 AN: 255440

Other (OTH) AF: 0.0000428 AC: 1 AN: 23358

GnomAD4 genome AF: 0.000125 AC: 17 AN: 136156 Hom.: 0 Cov.: 26 AF XY: 0.000138 AC XY: 9 AN XY: 65246

African (AFR) AF: 0.000110 AC: 4 AN: 36410

American (AMR) AF: 0.000236 AC: 3 AN: 12690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3328

East Asian (EAS) AF: 0.00 AC: 0 AN: 4624

South Asian (SAS) AF: 0.00 AC: 0 AN: 4346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000156 AC: 10 AN: 64024

Other (OTH) AF: 0.00 AC: 0 AN: 1944

Alfa AF: 0.00 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.27
PhyloP100		-0.18
PromoterAI		0.16	Neutral

Splicing

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

Publications

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Other links and lift over

dbSNP: rs4789430; hg19: chr17-75277430;