Genetic Variant ENST00000448879.5:c.-82-11449C>A (chr7-84206117-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448879.5(SEMA3A):c.-82-11449C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,014 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 352 hom., cov: 32)

Consequence

SEMA3A
ENST00000448879.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

4 publications found

Variant links:

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	XM_005250110.4 link	c.-82-11449C>A		intron_variant	Intron 3 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.-82-11449C>A		intron_variant	Intron 4 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000448879.5 link	c.-82-11449C>A		intron_variant	Intron 4 of 4	5		ENSP00000402093.1		A0A0C4DG50
SEMA3A	ENST00000424555.5 link	c.-82-11449C>A		intron_variant	Intron 3 of 3	4		ENSP00000404800.1		C9JD25

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9560

AN:

151896

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0921

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0527

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0629

AC:

9564

AN:

152014

Hom.:

352

Cov.:

AF XY:

0.0612

AC XY:

4551

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0921

AC:

3817

AN:

41462

American (AMR)

AF:

0.0526

AC:

802

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3468

East Asian (EAS)

AF:

0.000582

AC:

AN:

5156

South Asian (SAS)

AF:

0.0152

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0367

AC:

388

AN:

10562

Middle Eastern (MID)

AF:

0.0890

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0602

AC:

4091

AN:

67980

Other (OTH)

AF:

0.0739

AC:

156

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

447

893

1340

1786

2233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0581

Hom.:

156

Bravo

AF:

0.0670

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

1.4

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over