Genetic Variant SEMA3D:c.861+66_861+71dupATATAT (chr7-85055645-C-CATATAT) – 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+66_861+71dupATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 159,480 control chromosomes in the GnomAD database, including 32 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 32 hom., cov: 0)

Exomes 𝑓: 0.00089 ( 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 eas. GnomAd4 allele frequency = 0.0169 (1882/111350) while in subpopulation EAS AF = 0.0285 (102/3582). AF 95% confidence interval is 0.024. There are 32 homozygotes in GnomAd4. There are 891 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 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+66_861+71dupATATAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+66_861+71dupATATAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+66_861+71dupATATAT	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+72insATATAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insATATAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+71_861+72insATATAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

1881

AN:

111348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00900

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.0281

Gnomad FIN

AF:

0.00742

Gnomad MID

AF:

0.0196

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.0199

GnomAD4 exome

AF:

0.000893

AC:

AN:

48130

Hom.:

AF XY:

0.00104

AC XY:

AN XY:

27790

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:

690

American (AMR)

AF:

0.00517

AC:

AN:

774

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

712

East Asian (EAS)

AF:

0.00193

AC:

AN:

1034

South Asian (SAS)

AF:

0.00

AC:

AN:

1024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.000836

AC:

AN:

40660

Other (OTH)

AF:

0.00108

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: 0.291

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:

0.0169

AC:

1882

AN:

111350

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

891

AN XY:

51678

show subpopulations

African (AFR)

AF:

0.0102

AC:

310

AN:

30294

American (AMR)

AF:

0.0237

AC:

226

AN:

9518

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

2944

East Asian (EAS)

AF:

0.0285

AC:

102

AN:

3582

South Asian (SAS)

AF:

0.0282

AC:

AN:

2976

European-Finnish (FIN)

AF:

0.00742

AC:

AN:

3640

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.0185

AC:

1037

AN:

55956

Other (OTH)

AF:

0.0205

AC:

AN:

1466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

125

188

250

313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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

Splicing

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

Publications

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7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATAT

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