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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001384900.1(SEMA3D):c.861+68_861+71dupATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 159,224 control chromosomes in the GnomAD database, including 63 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 63 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 0 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0311 (3458/111142) while in subpopulation AMR AF = 0.0466 (442/9476). AF 95% confidence interval is 0.0431. There are 63 homozygotes in GnomAd4. There are 1564 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 63 AR gene

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+71dupATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+68_861+71dupATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+68_861+71dupATAT	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+71_861+72insATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+71_861+72insATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

3463

AN:

111140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00387

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0275

Gnomad EAS

AF:

0.0335

Gnomad SAS

AF:

0.0359

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.0385

Gnomad NFE

AF:

0.0358

Gnomad OTH

AF:

0.0337

GnomAD4 exome

AF:

0.00191

AC:

AN:

48082

Hom.:

AF XY:

0.00227

AC XY:

AN XY:

27754

show subpopulations

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

African (AFR)

AF:

0.00145

AC:

AN:

688

American (AMR)

AF:

0.00649

AC:

AN:

770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

710

East Asian (EAS)

AF:

0.00676

AC:

AN:

1036

South Asian (SAS)

AF:

0.00196

AC:

AN:

1022

European-Finnish (FIN)

AF:

0.00317

AC:

AN:

1262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00177

AC:

AN:

40620

Other (OTH)

AF:

0.000539

AC:

AN:

1856

⚠️ 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: 0.288

Heterozygous variant carriers

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:

0.0311

AC:

3458

AN:

111142

Hom.:

Cov.:

AF XY:

0.0303

AC XY:

1564

AN XY:

51592

show subpopulations

African (AFR)

AF:

0.0195

AC:

590

AN:

30274

American (AMR)

AF:

0.0466

AC:

442

AN:

9476

Ashkenazi Jewish (ASJ)

AF:

0.0275

AC:

AN:

2942

East Asian (EAS)

AF:

0.0337

AC:

120

AN:

3566

South Asian (SAS)

AF:

0.0357

AC:

106

AN:

2970

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

3610

Middle Eastern (MID)

AF:

0.0350

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.0358

AC:

2002

AN:

55864

Other (OTH)

AF:

0.0335

AC:

AN:

1464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATAT

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