Genetic Variant SEMA3A:c.1361-52T>A (chr7-84002098-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006080.3(SEMA3A):c.1361-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 984,588 control chromosomes in the GnomAD database, including 30,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4423 hom., cov: 33)

Exomes 𝑓: 0.25 ( 26476 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.328

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-84002098-A-T is Benign according to our data. Variant chr7-84002098-A-T is described in ClinVar as [Benign]. Clinvar id is 1231850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.1361-52T>A	intron_variant	Intron 11 of 16	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.1361-52T>A	intron_variant	Intron 14 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.1361-52T>A	intron_variant	Intron 15 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.1361-52T>A		intron_variant	Intron 11 of 16	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.1361-52T>A		intron_variant	Intron 12 of 17	5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36115

AN:

151976

Hom.:

4424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.241

AC:

51086

AN:

212320

Hom.:

6247

AF XY:

0.248

AC XY:

28645

AN XY:

115580

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.251

AC:

209220

AN:

832492

Hom.:

26476

Cov.:

AF XY:

0.254

AC XY:

111104

AN XY:

437968

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.238

AC:

36126

AN:

152096

Hom.:

4423

Cov.:

AF XY:

0.241

AC XY:

17921

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.178

Hom.:

544

Bravo

AF:

0.229

Asia WGS

AF:

0.234

AC:

816

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over