rs1357813

Positions:

• chr7-84060023-T-A
• chr7-84060023-T-G

Variant summary

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

The ENST00000265362.9(SEMA3A):​c.547+442A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,096 control chromosomes in the GnomAD database, including 6,620 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 0.29 (6620 hom., cov: 33)
• Consequence: SEMA3A ENST00000265362.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.547+442A>T		intron_variant		ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.547+442A>T		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.547+442A>T		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.547+442A>T		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000436949.5	c.547+442A>T		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43316 AN: 151980 Hom.: 6613 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152096 Hom.: 6620 Cov.: 33 AF XY: 0.287 AC XY: 21346 AN XY: 74356

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.275

Alfa AF: 0.272 Hom.: 749

Bravo AF: 0.292

Asia WGS AF: 0.255 AC: 891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs1357813; hg19: chr7-83689339;