Genetic Variant SEMA5B:c.-31T>C (chr3-122961294-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031702.4(SEMA5B):c.-31T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,324 control chromosomes in the GnomAD database, including 42,009 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 0.24 ( 4382 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37627 hom. )

Consequence

SEMA5B
NM_001031702.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0260

Publications

13 publications found

Variant links:

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SEMA5B links:

ENSG00000306095 (HGNC:):

ENSG00000306095 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5B	NM_001031702.4 link	c.-31T>C		5_prime_UTR_variant	Exon 2 of 23	ENST00000357599.8	NP_001026872.2	Q9P283-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5B	ENST00000357599.8 link	c.-31T>C		5_prime_UTR_variant	Exon 2 of 23	1	NM_001031702.4	ENSP00000350215.3		Q9P283-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35925

AN:

151974

Hom.:

4376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.244

AC:

60934

AN:

249638

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.389

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.224

AC:

327562

AN:

1460232

Hom.:

37627

Cov.:

AF XY:

0.223

AC XY:

162167

AN XY:

726428

show subpopulations

African (AFR)

AF:

0.240

AC:

8005

AN:

33420

American (AMR)

AF:

0.285

AC:

12686

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7339

AN:

26046

East Asian (EAS)

AF:

0.393

AC:

15588

AN:

39668

South Asian (SAS)

AF:

0.198

AC:

17009

AN:

86098

European-Finnish (FIN)

AF:

0.277

AC:

14785

AN:

53376

Middle Eastern (MID)

AF:

0.212

AC:

1219

AN:

5756

European-Non Finnish (NFE)

AF:

0.213

AC:

236708

AN:

1110990

Other (OTH)

AF:

0.236

AC:

14223

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

11964

23928

35892

47856

59820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8396

16792

25188

33584

41980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35949

AN:

152092

Hom.:

4382

Cov.:

AF XY:

0.243

AC XY:

18035

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.238

AC:

9884

AN:

41482

American (AMR)

AF:

0.262

AC:

4005

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1012

AN:

3472

East Asian (EAS)

AF:

0.373

AC:

1927

AN:

5162

South Asian (SAS)

AF:

0.207

AC:

997

AN:

4810

European-Finnish (FIN)

AF:

0.288

AC:

3048

AN:

10580

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14391

AN:

67968

Other (OTH)

AF:

0.233

AC:

492

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1420

2841

4261

5682

7102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

15566

Bravo

AF:

0.238

Asia WGS

AF:

0.244

AC:

848

AN:

3478

EpiCase

AF:

0.213

EpiControl

AF:

0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.2

(source)

DANN

Benign

0.66

PhyloP100

-0.026

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over