rs13231702

Positions:

• chr7-84194412-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006080.3(SEMA3A):​c.112+63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,071,794 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (352 hom., cov: 31)
  • Exomes 𝑓: 0.052 (1520 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.190

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-84194412-A-G is Benign according to our data. Variant chr7-84194412-A-G is described in ClinVar as [Benign]. Clinvar id is 1221861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.112+63T>C		intron_variant		ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.112+63T>C		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.112+63T>C		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.112+63T>C		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000420047.1	c.112+63T>C		intron_variant		4		ENSP00000391900
SEMA3A	ENST00000436949.5	c.112+63T>C		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 9547 AN: 116604 Hom.: 351 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0422

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.000671

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0973

GnomAD4 exome AF: 0.0524 AC: 50038 AN: 955092 Hom.: 1520 AF XY: 0.0508 AC XY: 25108 AN XY: 494230

Gnomad4 AFR exome AF: 0.0949

Gnomad4 AMR exome AF: 0.0403

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.0139

Gnomad4 FIN exome AF: 0.0376

Gnomad4 NFE exome AF: 0.0597

Gnomad4 OTH exome AF: 0.0536

GnomAD4 genome AF: 0.0818 AC: 9551 AN: 116702 Hom.: 352 Cov.: 31 AF XY: 0.0798 AC XY: 4552 AN XY: 57068

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.000673

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0495

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.0973

Alfa AF: 0.0648 Hom.: 46

Bravo AF: 0.0670

Asia WGS AF: 0.0140 AC: 51 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.75

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: rs13231702; hg19: chr7-83823728;