7-84315037-A-T

Variant names:

• chr7-84315037-A-T
• rs10488592
• ENST00000864988.1:c.-258-7745T>A

Variant summary

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

The ENST00000424555.5(SEMA3A):​c.-168-7745T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 152,278 control chromosomes in the GnomAD database, including 61 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 0.013 (61 hom., cov: 32)
• Consequence: SEMA3A ENST00000424555.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• 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, SD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000424555.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000864988.1		c.-258-7745T>A		intron	N/A	ENSP00000535047.1
	SEMA3A	ENST00000864989.1		c.-258-7745T>A		intron	N/A	ENSP00000535048.1
	SEMA3A	ENST00000864990.1		c.-258-7745T>A		intron	N/A	ENSP00000535049.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1912 AN: 152160 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.00207

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00762

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0126 AC: 1914 AN: 152278 Hom.: 61 Cov.: 32 AF XY: 0.0137 AC XY: 1018 AN XY: 74460

African (AFR) AF: 0.00204 AC: 85 AN: 41570

American (AMR) AF: 0.0155 AC: 237 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.145 AC: 751 AN: 5178

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4828

European-Finnish (FIN) AF: 0.00998 AC: 106 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00762 AC: 518 AN: 67998

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00402 Hom.: 0

Bravo AF: 0.0144

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10488592; hg19: chr7-83944353;