Genetic Variant SEMA3D:c.861+70_861+71delAT (chr7-85055645-CAT-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+70_861+71delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 158,572 control chromosomes in the GnomAD database, including 388 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.097 ( 384 hom., cov: 0)

Exomes 𝑓: 0.017 ( 4 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 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+70_861+71delAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+70_861+71delAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+70_861+71delAT	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+70_861+71delAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+70_861+71delAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+70_861+71delAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0969

AC:

10734

AN:

110790

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0552

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.0926

Gnomad EAS

AF:

0.0866

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0976

GnomAD4 exome

AF:

0.0170

AC:

813

AN:

47780

Hom.:

AF XY:

0.0181

AC XY:

500

AN XY:

27560

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

684

American (AMR)

AF:

0.0406

AC:

AN:

764

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

AN:

708

East Asian (EAS)

AF:

0.0223

AC:

AN:

1030

South Asian (SAS)

AF:

0.0187

AC:

AN:

1018

European-Finnish (FIN)

AF:

0.0338

AC:

AN:

1244

Middle Eastern (MID)

AF:

0.00862

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0160

AC:

646

AN:

40372

Other (OTH)

AF:

0.0201

AC:

AN:

1844

⚠️ 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: 0.335

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0968

AC:

10727

AN:

110792

Hom.:

384

Cov.:

AF XY:

0.0969

AC XY:

4977

AN XY:

51386

show subpopulations

African (AFR)

AF:

0.0552

AC:

1667

AN:

30222

American (AMR)

AF:

0.0930

AC:

884

AN:

9510

Ashkenazi Jewish (ASJ)

AF:

0.0926

AC:

272

AN:

2938

East Asian (EAS)

AF:

0.0866

AC:

309

AN:

3570

South Asian (SAS)

AF:

0.123

AC:

365

AN:

2964

European-Finnish (FIN)

AF:

0.142

AC:

504

AN:

3550

Middle Eastern (MID)

AF:

0.121

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.115

AC:

6383

AN:

55622

Other (OTH)

AF:

0.0968

AC:

141

AN:

1456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

340

680

1021

1361

1701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0913

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

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