rs17158675

Variant names:

• chr7-84153523-G-A
• rs17158675
• NM_006080.3:c.113-18572C>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.113-18572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,066 control chromosomes in the GnomAD database, including 773 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 0.077 (773 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.113-18572C>T		intron_variant	Intron 1 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.113-18572C>T		intron_variant	Intron 4 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.113-18572C>T		intron_variant	Intron 5 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.113-18572C>T		intron_variant	Intron 1 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.113-18572C>T		intron_variant	Intron 2 of 17	5		ENSP00000415260.1
SEMA3A	ENST00000420047.1	c.113-18572C>T		intron_variant	Intron 2 of 4	4		ENSP00000391900.1

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11700 AN: 151948 Hom.: 770 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0774

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0771 AC: 11718 AN: 152066 Hom.: 773 Cov.: 32 AF XY: 0.0756 AC XY: 5620 AN XY: 74366

African (AFR) AF: 0.171 AC: 7081 AN: 41432

American (AMR) AF: 0.0448 AC: 685 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0774 AC: 268 AN: 3464

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5178

South Asian (SAS) AF: 0.0755 AC: 364 AN: 4820

European-Finnish (FIN) AF: 0.0236 AC: 250 AN: 10588

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0407 AC: 2769 AN: 67994

Other (OTH) AF: 0.0769 AC: 162 AN: 2108

Alfa AF: 0.0562 Hom.: 890

Bravo AF: 0.0837

Asia WGS AF: 0.0610 AC: 212 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.28
PhyloP100		0.11
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: rs17158675; hg19: chr7-83782839;