17-77281348-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000589070.1(SEPTIN9):​c.31+542C>G variant causes a intron 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 ENST00000589070.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.183
• Publications: 2 publications found

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 -20 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 VariationId is 1248488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589070.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9-DT	NR_136503.1		n.286+264G>C		intron	N/A
	SEPTIN9	NM_001113491.2	MANE Select	c.-188C>G		upstream_gene	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.-188C>G		upstream_gene	N/A	NP_001280624.1	Q9UHD8-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000589070.1	TSL:3	c.31+542C>G		intron	N/A	ENSP00000465332.1	K7EJV0
	SEPTIN9-DT	ENST00000581153.1	TSL:2	n.286+264G>C		intron	N/A
	SEPTIN9-DT	ENST00000581657.2	TSL:3	n.491+264G>C		intron	N/A

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

African (AFR) AF: 0.0942 AC: 769 AN: 8160

American (AMR) AF: 0.110 AC: 1346 AN: 12234

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 3005 AN: 12120

East Asian (EAS) AF: 0.00449 AC: 106 AN: 23628

South Asian (SAS) AF: 0.102 AC: 4056 AN: 39898

European-Finnish (FIN) AF: 0.121 AC: 3435 AN: 28476

Middle Eastern (MID) AF: 0.197 AC: 363 AN: 1838

European-Non Finnish (NFE) AF: 0.167 AC: 42707 AN: 255198

Other (OTH) AF: 0.161 AC: 3749 AN: 23332

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

African (AFR) AF: 0.104 AC: 3784 AN: 36402

American (AMR) AF: 0.159 AC: 2015 AN: 12686

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 831 AN: 3328

East Asian (EAS) AF: 0.0106 AC: 49 AN: 4624

South Asian (SAS) AF: 0.104 AC: 453 AN: 4346

European-Finnish (FIN) AF: 0.156 AC: 1196 AN: 7656

Middle Eastern (MID) AF: 0.250 AC: 69 AN: 276

European-Non Finnish (NFE) AF: 0.176 AC: 11239 AN: 63988

Other (OTH) AF: 0.163 AC: 317 AN: 1942

Alfa AF: 0.0565 Hom.: 46

Bravo AF: 0.135

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.16
PhyloP100		-0.18
PromoterAI		0.19	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4789430; hg19: chr17-75277430;