7-84339187-C-T

Variant names:

• chr7-84339187-C-T
• rs10488587
• ENST00000864988.1:c.-258-31895G>A

Variant summary

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

The ENST00000424555.5(SEMA3A):​c.-168-31895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 151,780 control chromosomes in the GnomAD database, including 96 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 0.014 (96 hom., cov: 32)
• Consequence: SEMA3A ENST00000424555.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.-258-31895G>A		intron	N/A	ENSP00000535047.1
	SEMA3A	ENST00000864989.1		c.-258-31895G>A		intron	N/A	ENSP00000535048.1
	SEMA3A	ENST00000864990.1		c.-258-31895G>A		intron	N/A	ENSP00000535049.1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2201 AN: 151664 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00228

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0145 AC: 2197 AN: 151780 Hom.: 96 Cov.: 32 AF XY: 0.0161 AC XY: 1196 AN XY: 74214

African (AFR) AF: 0.00228 AC: 94 AN: 41310

American (AMR) AF: 0.0513 AC: 782 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.156 AC: 786 AN: 5034

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4820

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00388 AC: 264 AN: 67990

Other (OTH) AF: 0.0180 AC: 38 AN: 2108

Alfa AF: 0.00327 Hom.: 1

Bravo AF: 0.0189

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.47
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs10488587; hg19: chr7-83968503;