3-50159190-A-G

Position:

• chr3-50159190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318800.2(SEMA3F):​c.-147A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 165,192 control chromosomes in the GnomAD database, including 1,654 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 0.065 (1633 hom., cov: 33)
  • Exomes 𝑓: 0.015 (21 hom.)
• Consequence: SEMA3F NM_001318800.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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 (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.-48-385A>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.-48-385A>G		intron_variant		1	NM_004186.5	ENSP00000002829.3

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9857 AN: 152138 Hom.: 1631 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.0645

GnomAD4 exome AF: 0.0148 AC: 192 AN: 12936 Hom.: 21 Cov.: 0 AF XY: 0.0151 AC XY: 96 AN XY: 6348

Gnomad4 AFR exome AF: 0.0511

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.00303

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0279

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.0282

GnomAD4 genome AF: 0.0648 AC: 9867 AN: 152256 Hom.: 1633 Cov.: 33 AF XY: 0.0731 AC XY: 5445 AN XY: 74454

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.00344

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0217 Hom.: 85

Bravo AF: 0.0851

Asia WGS AF: 0.209 AC: 724 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	3.1
DANN	Benign	0.63

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: rs2072054; hg19: chr3-50196623;