chr7-84134993-C-G

Position:

• chr7-84134993-C-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.113-42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,558,342 control chromosomes in the GnomAD database, including 241,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20105 hom., cov: 32)
  • Exomes 𝑓: 0.56 (221638 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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=-0.82).
• BP6: Variant 7-84134993-C-G is Benign according to our data. Variant chr7-84134993-C-G is described in ClinVar as [Benign]. Clinvar id is 1266731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.113-42G>C		intron_variant		ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.113-42G>C		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.113-42G>C		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.113-42G>C		intron_variant		1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.113-42G>C		intron_variant		5		ENSP00000415260.1
SEMA3A	ENST00000420047.1	c.113-42G>C		intron_variant		4		ENSP00000391900.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76887 AN: 151836 Hom.: 20098 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.544

GnomAD3 exomes AF: 0.540 AC: 127271 AN: 235612 Hom.: 35131 AF XY: 0.537 AC XY: 68075 AN XY: 126708

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.696

Gnomad SAS exome AF: 0.440

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.558 AC: 784976 AN: 1406388 Hom.: 221638 Cov.: 22 AF XY: 0.556 AC XY: 389785 AN XY: 701030

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.506 AC: 76910 AN: 151954 Hom.: 20105 Cov.: 32 AF XY: 0.506 AC XY: 37600 AN XY: 74274

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.540

Alfa AF: 0.541 Hom.: 4103

Bravo AF: 0.507

Asia WGS AF: 0.529 AC: 1835 AN: 3478

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.57

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: rs17241389; hg19: chr7-83764309;