rs2189849

Positions:

• chr7-84062255-C-A
• chr7-84062255-C-G
• chr7-84062255-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.454-1697G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,050 control chromosomes in the GnomAD database, including 14,017 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 0.40 (14017 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.454-1697G>T		intron_variant		ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.454-1697G>T		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.454-1697G>T		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.454-1697G>T		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000436949.5	c.454-1697G>T		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61005 AN: 151934 Hom.: 13974 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.402 AC: 61098 AN: 152050 Hom.: 14017 Cov.: 33 AF XY: 0.403 AC XY: 29937 AN XY: 74320

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.370

Alfa AF: 0.305 Hom.: 8328

Bravo AF: 0.414

Asia WGS AF: 0.447 AC: 1556 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.43

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: rs2189849; hg19: chr7-83691571;