7-84188579-C-T

Variant names:

• chr7-84188579-C-T
• rs12707628
• NM_006080.3:c.112+5896G>A

Variant summary

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

The NM_006080.3(SEMA3A):​c.112+5896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,706 control chromosomes in the GnomAD database, including 10,797 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 0.37 (10797 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	NM_006080.3	MANE Select	c.112+5896G>A		intron	N/A	NP_006071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.112+5896G>A		intron	N/A	ENSP00000265362.3
	SEMA3A	ENST00000436949.5	TSL:5	c.112+5896G>A		intron	N/A	ENSP00000415260.1
	SEMA3A	ENST00000420047.1	TSL:4	c.112+5896G>A		intron	N/A	ENSP00000391900.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55425 AN: 151588 Hom.: 10789 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.366 AC: 55457 AN: 151706 Hom.: 10797 Cov.: 32 AF XY: 0.367 AC XY: 27176 AN XY: 74110

African (AFR) AF: 0.466 AC: 19324 AN: 41434

American (AMR) AF: 0.274 AC: 4168 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3072 AN: 5146

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4826

European-Finnish (FIN) AF: 0.323 AC: 3415 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21418 AN: 67760

Other (OTH) AF: 0.349 AC: 735 AN: 2108

Alfa AF: 0.327 Hom.: 7066

Bravo AF: 0.365

Asia WGS AF: 0.501 AC: 1735 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.16
PhyloP100		0.37
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: rs12707628; hg19: chr7-83817895;