rs2072053

Variant names:

• chr3-50159659-C-T
• rs2072053
• NM_004186.5:c.37C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-50159659-C-T
• chr3-50159659-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004186.5(SEMA3F):​c.37C>T​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,612,908 control chromosomes in the GnomAD database, including 11,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.054 (1579 hom., cov: 33)
  • Exomes 𝑓: 0.032 (10228 hom.)
• Consequence: SEMA3F NM_004186.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.92
• Publications: 8 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]

SEMA3F Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-50159659-C-T is Benign according to our data. Variant chr3-50159659-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060222.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004186.5. 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.37C>T	p.Leu13Leu	synonymous	Exon 2 of 19	NP_004177.3
	SEMA3F	NM_001318800.2		c.37C>T	p.Leu13Leu	synonymous	Exon 2 of 18	NP_001305729.1	Q13275-2
	SEMA3F	NM_001318798.2		c.-135-33C>T		intron	N/A	NP_001305727.1	C9JPG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3F	ENST00000002829.8	TSL:1 MANE Select	c.37C>T	p.Leu13Leu	synonymous	Exon 2 of 19	ENSP00000002829.3	Q13275-1
	SEMA3F	ENST00000434342.5	TSL:1	c.37C>T	p.Leu13Leu	synonymous	Exon 2 of 18	ENSP00000409859.1	Q13275-2
	SEMA3F	ENST00000413852.5	TSL:1	c.-135-33C>T		intron	N/A	ENSP00000388931.1	C9JPG5

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8205 AN: 152234 Hom.: 1578 Cov.: 33

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.0597

GnomAD2 exomes AF: 0.110 AC: 27343 AN: 249582 AF XY: 0.0906

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.00707

Gnomad EAS exome AF: 0.622

Gnomad FIN exome AF: 0.0472

Gnomad NFE exome AF: 0.00393

Gnomad OTH exome AF: 0.0627

GnomAD4 exome AF: 0.0325 AC: 47463 AN: 1460556 Hom.: 10228 Cov.: 29 AF XY: 0.0300 AC XY: 21767 AN XY: 726624

African (AFR) AF: 0.00475 AC: 159 AN: 33460

American (AMR) AF: 0.381 AC: 16940 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00777 AC: 203 AN: 26126

East Asian (EAS) AF: 0.548 AC: 21664 AN: 39518

South Asian (SAS) AF: 0.0117 AC: 1011 AN: 86142

European-Finnish (FIN) AF: 0.0474 AC: 2517 AN: 53138

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.00188 AC: 2094 AN: 1111612

Other (OTH) AF: 0.0473 AC: 2856 AN: 60352

GnomAD4 genome AF: 0.0539 AC: 8212 AN: 152352 Hom.: 1579 Cov.: 33 AF XY: 0.0623 AC XY: 4645 AN XY: 74502

African (AFR) AF: 0.00779 AC: 324 AN: 41584

American (AMR) AF: 0.243 AC: 3723 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3152 AN: 5178

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

European-Finnish (FIN) AF: 0.0492 AC: 523 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68042

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0119 Hom.: 98

Bravo AF: 0.0723

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3F-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		2.9
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: rs2072053; hg19: chr3-50197092;