dbSNP rs7780132: SEMA3D:c.1545+91G>A (chr7-85018161-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001384900.1(SEMA3D):c.1545+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 794,442 control chromosomes in the GnomAD database, including 120,812 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 0.58 ( 26333 hom., cov: 32)

Exomes 𝑓: 0.54 ( 94479 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

4 publications found

Variant links:

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) 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 like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

SEMA3D 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1 link	c.1545+91G>A		intron_variant	Intron 15 of 18	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11 link	c.1545+91G>A		intron_variant	Intron 15 of 18	5	NM_001384900.1	ENSP00000284136.6		O95025
SEMA3D	ENST00000484038.1 link	n.671+91G>A		intron_variant	Intron 6 of 9	1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87788

AN:

151308

Hom.:

26278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.592

GnomAD4 exome

AF:

0.537

AC:

345046

AN:

643016

Hom.:

94479

AF XY:

0.535

AC XY:

183965

AN XY:

343722

show subpopulations

African (AFR)

AF:

0.701

AC:

11297

AN:

16108

American (AMR)

AF:

0.497

AC:

16367

AN:

32924

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

11800

AN:

19844

East Asian (EAS)

AF:

0.697

AC:

23492

AN:

33722

South Asian (SAS)

AF:

0.518

AC:

32115

AN:

61986

European-Finnish (FIN)

AF:

0.378

AC:

18992

AN:

50218

Middle Eastern (MID)

AF:

0.546

AC:

2033

AN:

3722

European-Non Finnish (NFE)

AF:

0.538

AC:

210635

AN:

391768

Other (OTH)

AF:

0.560

AC:

18315

AN:

32724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7584

15168

22753

30337

37921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2562

5124

7686

10248

12810

<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:

0.581

AC:

87905

AN:

151426

Hom.:

26333

Cov.:

AF XY:

0.574

AC XY:

42437

AN XY:

73960

show subpopulations

African (AFR)

AF:

0.702

AC:

29042

AN:

41390

American (AMR)

AF:

0.565

AC:

8548

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2110

AN:

3456

East Asian (EAS)

AF:

0.732

AC:

3739

AN:

5106

South Asian (SAS)

AF:

0.527

AC:

2538

AN:

4814

European-Finnish (FIN)

AF:

0.376

AC:

3963

AN:

10550

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.531

AC:

35950

AN:

67656

Other (OTH)

AF:

0.593

AC:

1251

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1811

3622

5434

7245

9056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.555

Hom.:

36251

Bravo

AF:

0.599

Asia WGS

AF:

0.640

AC:

2223

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.8

(source)

DANN

Benign

0.46

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism (auto)

(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

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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