Genetic Variant SEMA4F:p.His61Arg (chr2-74656570-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004263.5(SEMA4F):c.182A>G(p.His61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SEMA4F
NM_004263.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.619

Publications

0 publications found

Variant links:

Genes affected

SEMA4F (HGNC:10734): (ssemaphorin 4F) This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SEMA4F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08170509).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004263.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEMA4F	NM_004263.5	MANE Select	c.182A>G	p.His61Arg	missense	Exon 2 of 14	NP_004254.2
SEMA4F	NM_001271662.2		c.182A>G	p.His61Arg	missense	Exon 2 of 13	NP_001258591.1
SEMA4F	NM_001271661.2		c.182A>G	p.His61Arg	missense	Exon 2 of 10	NP_001258590.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEMA4F	ENST00000357877.7	TSL:1 MANE Select	c.182A>G	p.His61Arg	missense	Exon 2 of 14	ENSP00000350547.2
SEMA4F	ENST00000339773.9	TSL:1	c.182A>G	p.His61Arg	missense	Exon 2 of 10	ENSP00000342675.5
SEMA4F	ENST00000420077.5	TSL:1	n.182A>G		non_coding_transcript_exon	Exon 2 of 12	ENSP00000416490.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.022

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.74

M_CAP

Benign

0.0049

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

PhyloP100

0.62

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.59

REVEL

Benign

0.040

Sift

Benign

0.13

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.19

MutPred

0.48

Gain of solvent accessibility (P = 0.0216)

MVP

0.19

MPC

0.27

ClinPred

0.84

GERP RS

2.3

Varity_R

0.042

gMVP

0.33

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over