rs2189849

Variant names:

• chr7-84062255-C-A
• rs2189849
• NM_006080.3:c.454-1697G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-84062255-C-A
• chr7-84062255-C-G
• chr7-84062255-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.454-1697G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,050 control chromosomes in the GnomAD database, including 14,017 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 0.40 (14017 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	NM_006080.3	MANE Select	c.454-1697G>T		intron	N/A	NP_006071.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.454-1697G>T		intron	N/A	ENSP00000265362.3
	SEMA3A	ENST00000436949.5	TSL:5	c.454-1697G>T		intron	N/A	ENSP00000415260.1
	SEMA3A	ENST00000864988.1		c.454-1697G>T		intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61005 AN: 151934 Hom.: 13974 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.402 AC: 61098 AN: 152050 Hom.: 14017 Cov.: 33 AF XY: 0.403 AC XY: 29937 AN XY: 74320

African (AFR) AF: 0.637 AC: 26434 AN: 41478

American (AMR) AF: 0.350 AC: 5335 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1799 AN: 5180

South Asian (SAS) AF: 0.470 AC: 2269 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2796 AN: 10560

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20123 AN: 67966

Other (OTH) AF: 0.370 AC: 778 AN: 2104

Alfa AF: 0.339 Hom.: 16209

Bravo AF: 0.414

Asia WGS AF: 0.447 AC: 1556 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		0.24
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: rs2189849; hg19: chr7-83691571;