rs12632110

Positions:

• chr3-50186792-A-G

Variant summary

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

The ENST00000002829.8(SEMA3F):​c.1947+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,523,090 control chromosomes in the GnomAD database, including 331,510 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 0.62 (29872 hom., cov: 32)
  • Exomes 𝑓: 0.66 (301638 hom.)
• Consequence: SEMA3F ENST00000002829.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.1947+46A>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.1947+46A>G		intron_variant		1	NM_004186.5	ENSP00000002829
SEMA3F	ENST00000413852.5	c.1650+46A>G		intron_variant		1		ENSP00000388931
SEMA3F	ENST00000434342.5	c.1854+46A>G		intron_variant		1		ENSP00000409859	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94143 AN: 151914 Hom.: 29841 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.633 AC: 112540 AN: 177694 Hom.: 37100 AF XY: 0.653 AC XY: 62712 AN XY: 96046

Gnomad AFR exome AF: 0.577

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.387

Gnomad SAS exome AF: 0.868

Gnomad FIN exome AF: 0.709

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.659 AC: 903940 AN: 1371058 Hom.: 301638 Cov.: 30 AF XY: 0.666 AC XY: 447331 AN XY: 671752

Gnomad4 AFR exome AF: 0.577

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.705

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome AF: 0.620 AC: 94227 AN: 152032 Hom.: 29872 Cov.: 32 AF XY: 0.621 AC XY: 46136 AN XY: 74312

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.617

Alfa AF: 0.641 Hom.: 61029

Bravo AF: 0.590

Asia WGS AF: 0.711 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.31

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: rs12632110; hg19: chr3-50224225; COSMIC: COSV50034294; COSMIC: COSV50034294;