rs917089

Variant names:

• chr7-84101133-C-A
• rs917089
• NM_006080.3:c.453+9337G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-84101133-C-A
• chr7-84101133-C-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+9337G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,938 control chromosomes in the GnomAD database, including 15,369 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 (15369 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.453+9337G>T		intron_variant	Intron 4 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.453+9337G>T		intron_variant	Intron 7 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.453+9337G>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+9337G>T		intron_variant	Intron 4 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.453+9337G>T		intron_variant	Intron 5 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65382 AN: 151820 Hom.: 15363 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.430 AC: 65406 AN: 151938 Hom.: 15369 Cov.: 32 AF XY: 0.432 AC XY: 32107 AN XY: 74248

African (AFR) AF: 0.222 AC: 9207 AN: 41444

American (AMR) AF: 0.527 AC: 8030 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3464

East Asian (EAS) AF: 0.479 AC: 2471 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4824

European-Finnish (FIN) AF: 0.523 AC: 5514 AN: 10550

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35206 AN: 67936

Other (OTH) AF: 0.466 AC: 985 AN: 2112

Alfa AF: 0.351 Hom.: 1291

Bravo AF: 0.428

Asia WGS AF: 0.357 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.19
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: rs917089; hg19: chr7-83730449;