dbSNP rs1543116: SEMA4B:c.322-8T>C (chr15-90217759-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198925.4(SEMA4B):c.322-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,610,618 control chromosomes in the GnomAD database, including 100,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 12101 hom., cov: 31)

Exomes 𝑓: 0.34 ( 88106 hom. )

Consequence

SEMA4B
NM_198925.4 splice_region, intron

Scores

Splicing: ADA: 0.00001581

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.800

Publications

14 publications found

Variant links:

Genes affected

SEMA4B (HGNC:10730): (semaphorin 4B) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Predicted to be involved in several processes, including generation of neurons; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4B 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4B	NM_198925.4 link	c.322-8T>C		splice_region_variant, intron_variant	Intron 2 of 13	ENST00000411539.7	NP_945119.1	Q9NPR2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4B	ENST00000411539.7 link	c.322-8T>C		splice_region_variant, intron_variant	Intron 2 of 13	1	NM_198925.4	ENSP00000394720.2		Q9NPR2-1

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59319

AN:

151760

Hom.:

12085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.370

GnomAD2 exomes

AF:

0.335

AC:

82621

AN:

246296

AF XY:

0.331

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.344

AC:

501776

AN:

1458740

Hom.:

88106

Cov.:

AF XY:

0.341

AC XY:

247496

AN XY:

725570

show subpopulations

African (AFR)

AF:

0.511

AC:

17076

AN:

33408

American (AMR)

AF:

0.309

AC:

13736

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9982

AN:

26090

East Asian (EAS)

AF:

0.214

AC:

8494

AN:

39662

South Asian (SAS)

AF:

0.242

AC:

20835

AN:

86084

European-Finnish (FIN)

AF:

0.423

AC:

22530

AN:

53302

Middle Eastern (MID)

AF:

0.325

AC:

1874

AN:

5764

European-Non Finnish (NFE)

AF:

0.348

AC:

386350

AN:

1109724

Other (OTH)

AF:

0.347

AC:

20899

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15183

30365

45548

60730

75913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12284

24568

36852

49136

61420

<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:

0.391

AC:

59361

AN:

151878

Hom.:

12101

Cov.:

AF XY:

0.389

AC XY:

28895

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.499

AC:

20649

AN:

41388

American (AMR)

AF:

0.337

AC:

5139

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1357

AN:

3466

East Asian (EAS)

AF:

0.196

AC:

1014

AN:

5176

South Asian (SAS)

AF:

0.238

AC:

1147

AN:

4822

European-Finnish (FIN)

AF:

0.433

AC:

4556

AN:

10528

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24315

AN:

67914

Other (OTH)

AF:

0.374

AC:

788

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1824

3648

5473

7297

9121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.361

Hom.:

20117

Bravo

AF:

0.390

Asia WGS

AF:

0.260

AC:

905

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.56

PhyloP100

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0020

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

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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