rs4732540

Variant names:

• chr7-84102336-G-A
• rs4732540
• NM_006080.3:c.453+8134C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006080.3(SEMA3A):​c.453+8134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,986 control chromosomes in the GnomAD database, including 15,026 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 0.43 (15026 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 1 publications found

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]

SEMA3A Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hypogonadotropic hypogonadism 16 with or without anosmia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.453+8134C>T		intron_variant	Intron 4 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.453+8134C>T		intron_variant	Intron 7 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.453+8134C>T		intron_variant	Intron 8 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.453+8134C>T		intron_variant	Intron 4 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.453+8134C>T		intron_variant	Intron 5 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65058 AN: 151868 Hom.: 15021 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.428 AC: 65082 AN: 151986 Hom.: 15026 Cov.: 32 AF XY: 0.429 AC XY: 31861 AN XY: 74282

African (AFR) AF: 0.235 AC: 9730 AN: 41462

American (AMR) AF: 0.530 AC: 8082 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2588 AN: 5154

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5171 AN: 10538

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34564 AN: 67968

Other (OTH) AF: 0.467 AC: 986 AN: 2112

Alfa AF: 0.462 Hom.: 2176

Bravo AF: 0.429

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4732540; hg19: chr7-83731652;