rs59186128

chr7-84160110-C-T

Variant summary

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

The NM_006080.3(SEMA3A):c.113-25159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,002 control chromosomes in the GnomAD database, including 653 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 0.063 (653 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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 = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.113-25159G>A		intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.113-25159G>A		intron_variant
SEMA3A	XM_047419751.1	c.113-25159G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.113-25159G>A		intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000420047.1	c.113-25159G>A		intron_variant		4
SEMA3A	ENST00000436949.5	c.113-25159G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9528 AN: 151884 Hom.: 650 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.00680

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0628 AC: 9547 AN: 152002 Hom.: 653 Cov.: 32 AF XY: 0.0615 AC XY: 4573 AN XY: 74320

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.00680

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0430 Hom.: 41

Bravo AF: 0.0687

Asia WGS AF: 0.0580 AC: 199 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.39
Dann	Benign	0.67

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: rs59186128; hg19: chr7-83789426;