Genetic Variant SEMA3D:c.861+50_861+71delATATATATATATATATATATAT (chr7-85055645-CATATATATATATATATATATAT-C) – 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+50_861+71delATATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 159,792 control chromosomes in the GnomAD database, including 6 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

SEMA3D
NM_001384900.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

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 links:

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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 afr. GnomAdExome4 allele frequency = 0.00197 (95/48148) while in subpopulation AFR AF = 0.042 (29/690). AF 95% confidence interval is 0.0301. There are 3 homozygotes in GnomAdExome4. There are 45 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1 link	c.861+50_861+71delATATATATATATATATATATAT		intron_variant	Intron 9 of 18	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SEMA3D	ENST00000284136.11 link	c.861+50_861+71delATATATATATATATATATATAT	intron_variant	Intron 9 of 18	5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000444867.1 link	c.861+50_861+71delATATATATATATATATATATAT	intron_variant	Intron 9 of 9	1		ENSP00000401366.1
SEMA3D	ENST00000463315.1 link	n.49+50_49+71delATATATATATATATATATATAT	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

351

AN:

111642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000553

Gnomad SAS

AF:

0.00133

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00481

Gnomad NFE

AF:

0.000268

Gnomad OTH

AF:

0.000687

GnomAD4 exome

AF:

0.00197

AC:

AN:

48148

Hom.:

AF XY:

0.00162

AC XY:

AN XY:

27800

show subpopulations

African (AFR)

AF:

0.0420

AC:

AN:

690

American (AMR)

AF:

0.00258

AC:

AN:

774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

710

East Asian (EAS)

AF:

0.00193

AC:

AN:

1038

South Asian (SAS)

AF:

0.00977

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:

0.00113

AC:

AN:

40672

Other (OTH)

AF:

0.00323

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.572

Heterozygous variant carriers

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:

0.00314

AC:

351

AN:

111644

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

167

AN XY:

51824

show subpopulations

African (AFR)

AF:

0.0103

AC:

314

AN:

30382

American (AMR)

AF:

0.00146

AC:

AN:

9572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2948

East Asian (EAS)

AF:

0.000556

AC:

AN:

3598

South Asian (SAS)

AF:

0.00134

AC:

AN:

2992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3644

Middle Eastern (MID)

AF:

0.00500

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000268

AC:

AN:

56062

Other (OTH)

AF:

0.000681

AC:

AN:

1468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.616

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Splicing

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

Publications

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7-85055645-CATATATATATATATATATATATATATATAT-CATATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over