rs11710277

Variant names:

• chr3-50162314-A-G
• rs11710277
• NM_004186.5:c.112+2580A>G

Variant summary

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

The NM_004186.5(SEMA3F):​c.112+2580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,338 control chromosomes in the GnomAD database, including 304 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 0.053 (304 hom., cov: 33)
• Consequence: SEMA3F NM_004186.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• Publications: 14 publications found

Genes affected

SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

SEMA3F Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004186.5. 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
	SEMA3F	NM_004186.5	MANE Select	c.112+2580A>G		intron	N/A	NP_004177.3
	SEMA3F	NM_001318800.2		c.112+2580A>G		intron	N/A	NP_001305729.1	Q13275-2
	SEMA3F	NM_001318798.2		c.-93+2580A>G		intron	N/A	NP_001305727.1	C9JPG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.112+2580A>G		intron	N/A	ENSP00000002829.3	Q13275-1
	SEMA3F	ENST00000434342.5	TSL:1	c.112+2580A>G		intron	N/A	ENSP00000409859.1	Q13275-2
	SEMA3F	ENST00000413852.5	TSL:1	c.-93+2580A>G		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8044 AN: 152220 Hom.: 304 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0528 AC: 8041 AN: 152338 Hom.: 304 Cov.: 33 AF XY: 0.0518 AC XY: 3859 AN XY: 74496

African (AFR) AF: 0.0147 AC: 612 AN: 41582

American (AMR) AF: 0.0450 AC: 689 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4828

European-Finnish (FIN) AF: 0.0786 AC: 835 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0769 AC: 5232 AN: 68014

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0697 Hom.: 680

Bravo AF: 0.0490

Asia WGS AF: 0.0110 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.73
PhyloP100		-0.85
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: rs11710277; hg19: chr3-50199747;