3-50159190-A-G

Variant names:

• chr3-50159190-A-G
• rs2072054
• ENST00000434342.5:c.-147A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318800.2. 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.-48-385A>G		intron	N/A	NP_004177.3
	SEMA3F	NM_001318800.2		c.-147A>G		5_prime_UTR	Exon 1 of 18	NP_001305729.1
	SEMA3F	NM_001318798.2		c.-135-502A>G		intron	N/A	NP_001305727.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3F	ENST00000434342.5	TSL:1	c.-147A>G		5_prime_UTR	Exon 1 of 18	ENSP00000409859.1
	SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.-48-385A>G		intron	N/A	ENSP00000002829.3
	SEMA3F	ENST00000413852.5	TSL:1	c.-135-502A>G		intron	N/A	ENSP00000388931.1

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

African (AFR) AF: 0.0511 AC: 9 AN: 176

American (AMR) AF: 0.149 AC: 20 AN: 134

Ashkenazi Jewish (ASJ) AF: 0.00303 AC: 1 AN: 330

East Asian (EAS) AF: 0.471 AC: 64 AN: 136

South Asian (SAS) AF: 0.0102 AC: 9 AN: 884

European-Finnish (FIN) AF: 0.0279 AC: 20 AN: 718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 82

European-Non Finnish (NFE) AF: 0.00459 AC: 44 AN: 9588

Other (OTH) AF: 0.0282 AC: 25 AN: 888

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

African (AFR) AF: 0.0456 AC: 1896 AN: 41560

American (AMR) AF: 0.247 AC: 3779 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3162 AN: 5166

South Asian (SAS) AF: 0.0217 AC: 105 AN: 4828

European-Finnish (FIN) AF: 0.0492 AC: 522 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00344 AC: 234 AN: 68004

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0194 Hom.: 168

Bravo AF: 0.0851

Asia WGS AF: 0.209 AC: 724 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	3.1
DANN	Benign	0.63
PhyloP100		-0.18
PromoterAI		0.017	Neutral
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: rs2072054; hg19: chr3-50196623;