rs2527039

Variant names:

• chr7-84060298-C-T
• rs2527039
• NM_006080.3:c.547+167G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006080.3(SEMA3A):​c.547+167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,008 control chromosomes in the GnomAD database, including 6,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6624 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-84060298-C-T is Benign according to our data. Variant chr7-84060298-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.547+167G>A		intron_variant	Intron 5 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.547+167G>A		intron_variant	Intron 8 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.547+167G>A		intron_variant	Intron 9 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.547+167G>A		intron_variant	Intron 5 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.547+167G>A		intron_variant	Intron 6 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43313 AN: 151888 Hom.: 6616 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152008 Hom.: 6624 Cov.: 33 AF XY: 0.287 AC XY: 21333 AN XY: 74294

African (AFR) AF: 0.392 AC: 16236 AN: 41468

American (AMR) AF: 0.284 AC: 4331 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5180

South Asian (SAS) AF: 0.355 AC: 1707 AN: 4814

European-Finnish (FIN) AF: 0.225 AC: 2378 AN: 10562

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16087 AN: 67942

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.254 Hom.: 7770

Bravo AF: 0.292

Asia WGS AF: 0.255 AC: 892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.31
PhyloP100		0.18
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: rs2527039; hg19: chr7-83689614;