7-83977202-G-A

Position:

• chr7-83977202-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_006080.3(SEMA3A):​c.1653-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,552,192 control chromosomes in the GnomAD database, including 485,009 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52439 hom., cov: 31)
  • Exomes 𝑓: 0.78 (432570 hom.)
• Consequence: SEMA3A NM_006080.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007299
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-83977202-G-A is Benign according to our data. Variant chr7-83977202-G-A is described in ClinVar as [Benign]. Clinvar id is 1174901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83977202-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.1653-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.1653-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SEMA3A	XM_047419751.1	c.1653-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1653-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.1653-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125272 AN: 151856 Hom.: 52367 Cov.: 31

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.827

GnomAD3 exomes AF: 0.788 AC: 186776 AN: 236956 Hom.: 74353 AF XY: 0.780 AC XY: 100379 AN XY: 128716

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 0.898

Gnomad SAS exome AF: 0.743

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.784 AC: 1098096 AN: 1400220 Hom.: 432570 Cov.: 23 AF XY: 0.783 AC XY: 546392 AN XY: 697954

Gnomad4 AFR exome AF: 0.964

Gnomad4 AMR exome AF: 0.828

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.788

GnomAD4 genome AF: 0.825 AC: 125406 AN: 151972 Hom.: 52439 Cov.: 31 AF XY: 0.817 AC XY: 60700 AN XY: 74278

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.830

Alfa AF: 0.785 Hom.: 109200

Bravo AF: 0.843

Asia WGS AF: 0.851 AC: 2957 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.052
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

Other links and lift over

dbSNP: rs701320; hg19: chr7-83606518;