rs3735513

chr7-84002060-T-Cchr7-84002060-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006080.3(SEMA3A):c.1361-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,509,330 control chromosomes in the GnomAD database, including 42,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4460 hom., cov: 33)
  • Exomes 𝑓: 0.24 (38394 hom.)
• Consequence: SEMA3A NM_006080.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-84002060-T-C is Benign according to our data. Variant chr7-84002060-T-C is described in ClinVar as [Benign]. Clinvar id is 1601502.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-84002060-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.1361-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.1361-14A>G		splice_polypyrimidine_tract_variant, intron_variant
SEMA3A	XM_047419751.1	c.1361-14A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.1361-14A>G		splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36236 AN: 151930 Hom.: 4461 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.231

GnomAD3 exomes AF: 0.237 AC: 58101 AN: 244654 Hom.: 7271 AF XY: 0.245 AC XY: 32532 AN XY: 132620

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.321

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.236 AC: 320433 AN: 1357282 Hom.: 38394 Cov.: 20 AF XY: 0.239 AC XY: 162659 AN XY: 681322

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.238 AC: 36249 AN: 152048 Hom.: 4460 Cov.: 33 AF XY: 0.242 AC XY: 17988 AN XY: 74334

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.230

Alfa AF: 0.239 Hom.: 2739

Bravo AF: 0.230

Asia WGS AF: 0.237 AC: 827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.31
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3735513; hg19: chr7-83631376; COSMIC: COSV54864780;