7-84325421-A-C

Variant names:

• chr7-84325421-A-C
• rs6467991
• ENST00000448879.5:c.-168-18129T>G

Variant summary

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

The ENST00000448879.5(SEMA3A):​c.-168-18129T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,860 control chromosomes in the GnomAD database, including 8,409 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 0.28 (8409 hom., cov: 31)
• Consequence: SEMA3A ENST00000448879.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448879.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000448879.5	TSL:5	c.-168-18129T>G		intron	N/A	ENSP00000402093.1
	SEMA3A	ENST00000424555.5	TSL:4	c.-168-18129T>G		intron	N/A	ENSP00000404800.1
	SEMA3A	ENST00000471474.5	TSL:5	n.373-18129T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42853 AN: 151740 Hom.: 8388 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.283 AC: 42924 AN: 151860 Hom.: 8409 Cov.: 31 AF XY: 0.282 AC XY: 20960 AN XY: 74206

African (AFR) AF: 0.550 AC: 22767 AN: 41362

American (AMR) AF: 0.190 AC: 2899 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2005 AN: 5128

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2170 AN: 10548

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10282 AN: 67948

Other (OTH) AF: 0.264 AC: 556 AN: 2110

Alfa AF: 0.188 Hom.: 6910

Bravo AF: 0.295

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.0
DANN	Benign	0.78
PhyloP100		-0.056

Splicing

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

Other links and lift over

dbSNP: rs6467991; hg19: chr7-83954737;