rs758377

Variant names:

• chr17-58529763-T-C
• rs758377
• NM_001368771.2:c.1615-2785A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-58529763-T-C
• chr17-58529763-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368771.2(SEPTIN4):​c.1615-2785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,548 control chromosomes in the GnomAD database, including 53,813 homozygotes. 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 0.84 (53794 hom., cov: 29)
  • Exomes 𝑓: 0.77 (19 hom.)
• Consequence: SEPTIN4 NM_001368771.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 5 publications found

Genes affected

SEPTIN4 (HGNC:9165): (septin 4) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368771.2. 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
	SEPTIN4	NM_001368771.2	MANE Select	c.1615-2785A>G		intron	N/A	NP_001355700.1	O43236-7
	SEPTIN4	NM_001256782.2		c.106-2785A>G		intron	N/A	NP_001243711.1	O43236-4
	SEPTIN4	NM_001368772.2		c.40-2785A>G		intron	N/A	NP_001355701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN4	ENST00000672673.2	MANE Select	c.1615-2785A>G		intron	N/A	ENSP00000500383.1	O43236-7
	SEPTIN4	ENST00000317256.10	TSL:1	c.3+2198A>G		intron	N/A	ENSP00000321071.6	O43236-2
	SEPTIN4	ENST00000426861.5	TSL:1	c.3+2198A>G		intron	N/A	ENSP00000402348.1	O43236-6

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127249 AN: 151374 Hom.: 53730 Cov.: 29

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.808

GnomAD4 exome AF: 0.767 AC: 46 AN: 60 Hom.: 19 AF XY: 0.737 AC XY: 28 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.760 AC: 38 AN: 50

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.841 AC: 127372 AN: 151488 Hom.: 53794 Cov.: 29 AF XY: 0.844 AC XY: 62411 AN XY: 73930

African (AFR) AF: 0.909 AC: 37493 AN: 41226

American (AMR) AF: 0.847 AC: 12924 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2704 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5154 AN: 5164

South Asian (SAS) AF: 0.900 AC: 4327 AN: 4810

European-Finnish (FIN) AF: 0.831 AC: 8574 AN: 10320

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53512 AN: 67928

Other (OTH) AF: 0.810 AC: 1706 AN: 2106

Alfa AF: 0.798 Hom.: 18360

Bravo AF: 0.844

Asia WGS AF: 0.955 AC: 3321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.56
PhyloP100		-1.7
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs758377; hg19: chr17-56607124;