rs473880

Positions:

• chr7-84279764-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448879.5(SEMA3A):​c.-83+27443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,072 control chromosomes in the GnomAD database, including 16,105 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 0.45 (16105 hom., cov: 34)
• Consequence: SEMA3A ENST00000448879.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	XM_005250110.4	c.-83+27443C>T		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.-83+15278C>T		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000424555.5	c.-83+27443C>T		intron_variant		4		ENSP00000404800
SEMA3A	ENST00000448879.5	c.-83+27443C>T		intron_variant		5		ENSP00000402093

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67818 AN: 151954 Hom.: 16100 Cov.: 34

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.446 AC: 67841 AN: 152072 Hom.: 16105 Cov.: 34 AF XY: 0.444 AC XY: 33016 AN XY: 74330

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.472

Alfa AF: 0.510 Hom.: 8770

Bravo AF: 0.438

Asia WGS AF: 0.547 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs473880; hg19: chr7-83909080;