Genetic Variant SEMA3D:c.861+70_861+71dupAT (chr7-85055645-C-CAT) – 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+71dupAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 159,026 control chromosomes in the GnomAD database, including 116 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 116 hom., cov: 0)

Exomes 𝑓: 0.0042 ( 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:

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ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0509 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+71dupAT	intron	N/A	NP_001371829.1	O95025
SEMA3D	NM_001384901.1		c.861+70_861+71dupAT	intron	N/A	NP_001371830.1	O95025
SEMA3D	NM_001384902.1		c.861+70_861+71dupAT	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+72insAT	intron	N/A	ENSP00000284136.6	O95025
SEMA3D	ENST00000444867.1	TSL:1	c.861+71_861+72insAT	intron	N/A	ENSP00000401366.1	C9JYT6
SEMA3D	ENST00000916323.1		c.861+71_861+72insAT	intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

4605

AN:

111008

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0438

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0960

Gnomad EAS

AF:

0.0389

Gnomad SAS

AF:

0.0477

Gnomad FIN

AF:

0.0251

Gnomad MID

AF:

0.0294

Gnomad NFE

AF:

0.0525

Gnomad OTH

AF:

0.0500

GnomAD4 exome

AF:

0.00417

AC:

200

AN:

48016

Hom.:

AF XY:

0.00466

AC XY:

129

AN XY:

27704

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:

0.00904

AC:

AN:

774

Ashkenazi Jewish (ASJ)

AF:

0.00562

AC:

AN:

712

East Asian (EAS)

AF:

0.00578

AC:

AN:

1038

South Asian (SAS)

AF:

0.00391

AC:

AN:

1022

European-Finnish (FIN)

AF:

0.00874

AC:

AN:

1258

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00392

AC:

159

AN:

40552

Other (OTH)

AF:

0.00324

AC:

AN:

1854

⚠️ 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: 0.309

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:

0.0415

AC:

4603

AN:

111010

Hom.:

116

Cov.:

AF XY:

0.0402

AC XY:

2073

AN XY:

51504

show subpopulations

African (AFR)

AF:

0.0153

AC:

464

AN:

30296

American (AMR)

AF:

0.0470

AC:

446

AN:

9480

Ashkenazi Jewish (ASJ)

AF:

0.0960

AC:

280

AN:

2916

East Asian (EAS)

AF:

0.0391

AC:

140

AN:

3578

South Asian (SAS)

AF:

0.0478

AC:

142

AN:

2968

European-Finnish (FIN)

AF:

0.0251

AC:

AN:

3590

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.0525

AC:

2928

AN:

55758

Other (OTH)

AF:

0.0503

AC:

AN:

1452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

153

306

460

613

766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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-CATATATATATATATATATATATATATATATAT

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