Genetic Variant SEMA3D:c.861+52_861+71delATATATATATATATATATAT (chr7-85055645-CATATATATATATATATATAT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001384900.1(SEMA3D):c.861+52_861+71delATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 159,482 control chromosomes in the GnomAD database, including 3 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 0.00069 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0063 ( 1 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 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
SEMA3D	NM_001384900.1	MANE Select	c.861+52_861+71delATATATATATATATATATAT	intron	N/A	NP_001371829.1
SEMA3D	NM_001384901.1		c.861+52_861+71delATATATATATATATATATAT	intron	N/A	NP_001371830.1
SEMA3D	NM_001384902.1		c.861+52_861+71delATATATATATATATATATAT	intron	N/A	NP_001371831.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.861+52_861+71delATATATATATATATATATAT	intron	N/A	ENSP00000284136.6
SEMA3D	ENST00000444867.1	TSL:1	c.861+52_861+71delATATATATATATATATATAT	intron	N/A	ENSP00000401366.1
SEMA3D	ENST00000463315.1	TSL:2	n.49+52_49+71delATATATATATATATATATAT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

AN:

111640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000829

Gnomad SAS

AF:

0.000999

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000268

Gnomad OTH

AF:

0.00137

GnomAD4 exome

AF:

0.00627

AC:

300

AN:

47840

Hom.:

AF XY:

0.00634

AC XY:

175

AN XY:

27604

show subpopulations

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

African (AFR)

AF:

0.0117

AC:

AN:

686

American (AMR)

AF:

0.00391

AC:

AN:

768

Ashkenazi Jewish (ASJ)

AF:

0.00712

AC:

AN:

702

East Asian (EAS)

AF:

0.000965

AC:

AN:

1036

South Asian (SAS)

AF:

0.00491

AC:

AN:

1018

European-Finnish (FIN)

AF:

0.00879

AC:

AN:

1252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00626

AC:

253

AN:

40408

Other (OTH)

AF:

0.00756

AC:

AN:

1852

⚠️ 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: 0.305

Heterozygous variant carriers

102

127

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:

0.000690

AC:

AN:

111642

Hom.:

Cov.:

AF XY:

0.000791

AC XY:

AN XY:

51824

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

30380

American (AMR)

AF:

0.000313

AC:

AN:

9572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2948

East Asian (EAS)

AF:

0.000834

AC:

AN:

3598

South Asian (SAS)

AF:

0.00100

AC:

AN:

2992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.000268

AC:

AN:

56062

Other (OTH)

AF:

0.00204

AC:

AN:

1468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.589

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

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-CATATATATAT

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