Genetic Variant SEMA3D:c.589+37G>A (chr7-85068154-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.589+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,198,262 control chromosomes in the GnomAD database, including 516 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 0.035 ( 320 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 196 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.306

Publications

2 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1 link	c.589+37G>A		intron_variant	Intron 7 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.589+37G>A		intron_variant	Intron 7 of 18	5	NM_001384900.1	ENSP00000284136.6		O95025
SEMA3D	ENST00000444867.1 link	c.589+37G>A		intron_variant	Intron 7 of 9	1		ENSP00000401366.1		C9JYT6

Frequencies

GnomAD3 genomes

AF:

0.0352

AC:

5354

AN:

151992

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.00947

AC:

2250

AN:

237708

AF XY:

0.00690

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.00575

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00370

AC:

3875

AN:

1046152

Hom.:

196

Cov.:

AF XY:

0.00310

AC XY:

1670

AN XY:

538214

show subpopulations

African (AFR)

AF:

0.125

AC:

3102

AN:

24726

American (AMR)

AF:

0.00643

AC:

265

AN:

41244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22920

East Asian (EAS)

AF:

0.00

AC:

AN:

37578

South Asian (SAS)

AF:

0.000199

AC:

AN:

75286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52690

Middle Eastern (MID)

AF:

0.00633

AC:

AN:

4894

European-Non Finnish (NFE)

AF:

0.000122

AC:

AN:

740280

Other (OTH)

AF:

0.00799

AC:

372

AN:

46534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

159

317

476

634

793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0353

AC:

5367

AN:

152110

Hom.:

320

Cov.:

AF XY:

0.0336

AC XY:

2500

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.121

AC:

5033

AN:

41496

American (AMR)

AF:

0.0158

AC:

242

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

67964

Other (OTH)

AF:

0.0270

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

251

502

752

1003

1254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0196

Hom.:

Bravo

AF:

0.0406

Asia WGS

AF:

0.00578

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.73

PhyloP100

-0.31

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