NM_004186.5:c.1947+46A>G

Variant names:

• chr3-50186792-A-G
• rs12632110
• NM_004186.5:c.1947+46A>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.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 NM_004186.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 27 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEMA3F	NM_004186.5	c.1947+46A>G		intron_variant	Intron 18 of 18	ENST00000002829.8	NP_004177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3F	ENST00000002829.8	c.1947+46A>G		intron_variant	Intron 18 of 18	1	NM_004186.5	ENSP00000002829.3
SEMA3F	ENST00000434342.5	c.1854+46A>G		intron_variant	Intron 17 of 17	1		ENSP00000409859.1
SEMA3F	ENST00000413852.5	c.1650+46A>G		intron_variant	Intron 17 of 17	1		ENSP00000388931.1

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

GnomAD2 exomes AF: 0.633 AC: 112540 AN: 177694 AF XY: 0.653

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 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

African (AFR) AF: 0.577 AC: 18204 AN: 31524

American (AMR) AF: 0.434 AC: 14851 AN: 34190

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 15921 AN: 23100

East Asian (EAS) AF: 0.462 AC: 16950 AN: 36700

South Asian (SAS) AF: 0.865 AC: 66463 AN: 76800

European-Finnish (FIN) AF: 0.705 AC: 35286 AN: 50054

Middle Eastern (MID) AF: 0.667 AC: 3642 AN: 5462

European-Non Finnish (NFE) AF: 0.659 AC: 696146 AN: 1056860

Other (OTH) AF: 0.647 AC: 36477 AN: 56368

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

African (AFR) AF: 0.578 AC: 23963 AN: 41462

American (AMR) AF: 0.475 AC: 7246 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3472

East Asian (EAS) AF: 0.389 AC: 2007 AN: 5158

South Asian (SAS) AF: 0.863 AC: 4159 AN: 4822

European-Finnish (FIN) AF: 0.703 AC: 7429 AN: 10570

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44871 AN: 67968

Other (OTH) AF: 0.617 AC: 1304 AN: 2114

Alfa AF: 0.636 Hom.: 95086

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
PhyloP100		-1.2
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: rs12632110; hg19: chr3-50224225; COSMIC: COSV50034294; COSMIC: COSV50034294;