rs11976275

Positions:

• chr7-84206117-G-T

Variant summary

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

The ENST00000448879.5(SEMA3A):​c.-82-11449C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,014 control chromosomes in the GnomAD database, including 352 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 (352 hom., cov: 32)
• Consequence: SEMA3A ENST00000448879.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	XM_005250110.4	c.-82-11449C>A		intron_variant
SEMA3A	XM_047419751.1	c.-82-11449C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000424555.5	c.-82-11449C>A		intron_variant		4
SEMA3A	ENST00000448879.5	c.-82-11449C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9560 AN: 151896 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0747

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

GnomAD4 genome AF: 0.0629 AC: 9564 AN: 152014 Hom.: 352 Cov.: 32 AF XY: 0.0612 AC XY: 4551 AN XY: 74338

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0152

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0580 Hom.: 141

Bravo AF: 0.0670

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11976275; hg19: chr7-83835433;