rs2272221

chr7-84014371-G-A

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.668-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,560,980 control chromosomes in the GnomAD database, including 95,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16120 hom., cov: 32)
  • Exomes 𝑓: 0.33 (79324 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.188

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=-0.85).
• BP6: Variant 7-84014371-G-A is Benign according to our data. Variant chr7-84014371-G-A is described in ClinVar as [Benign]. Clinvar id is 1174858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-84014371-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.668-20C>T		intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.668-20C>T		intron_variant
SEMA3A	XM_047419751.1	c.668-20C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.668-20C>T		intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.668-20C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65317 AN: 151406 Hom.: 16094 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.395

GnomAD3 exomes AF: 0.366 AC: 89518 AN: 244800 Hom.: 17328 AF XY: 0.364 AC XY: 48298 AN XY: 132606

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.343

Gnomad SAS exome AF: 0.462

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.326 AC: 459567 AN: 1409458 Hom.: 79324 Cov.: 26 AF XY: 0.329 AC XY: 231716 AN XY: 703954

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.432 AC: 65395 AN: 151522 Hom.: 16120 Cov.: 32 AF XY: 0.433 AC XY: 32023 AN XY: 74022

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.395

Alfa AF: 0.370 Hom.: 2134

Bravo AF: 0.443

Asia WGS AF: 0.440 AC: 1531 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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	-0.85
Cadd	Benign	6.8
Dann	Benign	0.63

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: rs2272221; hg19: chr7-83643687;