rs11710277

Positions:

• chr3-50162314-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.112+2580A>G		intron_variant		ENST00000002829.8	NP_004177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3F	ENST00000002829.8	c.112+2580A>G		intron_variant		1	NM_004186.5	ENSP00000002829.3

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

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.0786

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0722 Hom.: 479

Bravo AF: 0.0490

Asia WGS AF: 0.0110 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.73

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: rs11710277; hg19: chr3-50199747;