Genetic Variant SEMA3D:c.861+68_861+71delATAT (chr7-85055645-CATAT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384900.1(SEMA3D):c.861+68_861+71delATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 159,060 control chromosomes in the GnomAD database, including 248 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.067 ( 247 hom., cov: 0)

Exomes 𝑓: 0.018 ( 1 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

Publications

1 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 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.861+68_861+71delATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+68_861+71delATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+68_861+71delATAT	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.861+68_861+71delATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+68_861+71delATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+68_861+71delATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

7435

AN:

111262

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.0180

Gnomad AMR

AF:

0.0859

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.0631

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0591

GnomAD4 exome

AF:

0.0179

AC:

854

AN:

47796

Hom.:

AF XY:

0.0192

AC XY:

529

AN XY:

27588

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0205

AC:

AN:

682

American (AMR)

AF:

0.0313

AC:

AN:

768

Ashkenazi Jewish (ASJ)

AF:

0.0226

AC:

AN:

708

East Asian (EAS)

AF:

0.0489

AC:

AN:

1022

South Asian (SAS)

AF:

0.0287

AC:

AN:

1012

European-Finnish (FIN)

AF:

0.0319

AC:

AN:

1254

Middle Eastern (MID)

AF:

0.00862

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0158

AC:

640

AN:

40382

Other (OTH)

AF:

0.0216

AC:

AN:

1852

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.341

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0669

AC:

7438

AN:

111264

Hom.:

247

Cov.:

AF XY:

0.0667

AC XY:

3442

AN XY:

51636

show subpopulations

African (AFR)

AF:

0.0632

AC:

1911

AN:

30244

American (AMR)

AF:

0.0861

AC:

821

AN:

9530

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

300

AN:

2928

East Asian (EAS)

AF:

0.114

AC:

408

AN:

3584

South Asian (SAS)

AF:

0.110

AC:

328

AN:

2984

European-Finnish (FIN)

AF:

0.0522

AC:

189

AN:

3622

Middle Eastern (MID)

AF:

0.0606

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.0602

AC:

3369

AN:

55930

Other (OTH)

AF:

0.0587

AC:

AN:

1466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

243

485

728

970

1213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0440

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over