Genetic Variant SEMA3D:c.1703+29G>C (chr7-85015030-C-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_001384900.1(SEMA3D):c.1703+29G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,569,928 control chromosomes in the GnomAD database, including 249,978 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 0.59 ( 27616 hom., cov: 32)

Exomes 𝑓: 0.56 ( 222362 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

14 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 Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

SEMA3D links:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3D	NM_001384900.1	MANE Select	c.1703+29G>C	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.1703+29G>C	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.1703+29G>C	intron	N/A	NP_001371831.1	O95025

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.1703+29G>C	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000484038.1	TSL:1	n.829+29G>C	intron	N/A
SEMA3D	ENST00000916323.1		c.1703+29G>C	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

89939

AN:

151436

Hom.:

27559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.612

GnomAD2 exomes

AF:

0.564

AC:

138480

AN:

245654

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.543

Gnomad ASJ exome

AF:

0.604

Gnomad EAS exome

AF:

0.756

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.556

AC:

788907

AN:

1418374

Hom.:

222362

Cov.:

AF XY:

0.557

AC XY:

392299

AN XY:

704430

show subpopulations

African (AFR)

AF:

0.710

AC:

23053

AN:

32452

American (AMR)

AF:

0.549

AC:

23992

AN:

43668

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

15307

AN:

25176

East Asian (EAS)

AF:

0.721

AC:

28208

AN:

39138

South Asian (SAS)

AF:

0.590

AC:

49643

AN:

84176

European-Finnish (FIN)

AF:

0.375

AC:

19829

AN:

52922

Middle Eastern (MID)

AF:

0.583

AC:

3267

AN:

5600

European-Non Finnish (NFE)

AF:

0.550

AC:

591814

AN:

1076596

Other (OTH)

AF:

0.576

AC:

33794

AN:

58646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14946

29892

44837

59783

74729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16920

33840

50760

67680

84600

<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:

0.594

AC:

90060

AN:

151554

Hom.:

27616

Cov.:

AF XY:

0.589

AC XY:

43588

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.704

AC:

29142

AN:

41392

American (AMR)

AF:

0.614

AC:

9326

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2153

AN:

3460

East Asian (EAS)

AF:

0.753

AC:

3838

AN:

5094

South Asian (SAS)

AF:

0.604

AC:

2913

AN:

4824

European-Finnish (FIN)

AF:

0.370

AC:

3901

AN:

10544

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36726

AN:

67742

Other (OTH)

AF:

0.613

AC:

1293

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1777

3554

5331

7108

8885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.478

Hom.:

2423

Bravo

AF:

0.614

Asia WGS

AF:

0.697

AC:

2425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.51

(source)

DANN

Benign

0.39

PhyloP100

-1.5

Mutation Taster

=9/91

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over