chr7-84002201-T-C

Variant names:

• chr7-84002201-T-C
• rs3735514
• NM_006080.3:c.1361-155A>G

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.1361-155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,082 control chromosomes in the GnomAD database, including 4,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4306 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760
• Publications: 2 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=-0.78).
• BP6: Variant 7-84002201-T-C is Benign according to our data. Variant chr7-84002201-T-C is described in ClinVar as Benign. ClinVar VariationId is 1234621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1361-155A>G		intron_variant	Intron 11 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1361-155A>G		intron_variant	Intron 14 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1361-155A>G		intron_variant	Intron 15 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-155A>G		intron_variant	Intron 11 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1361-155A>G		intron_variant	Intron 12 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35661 AN: 151964 Hom.: 4307 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.235 AC: 35670 AN: 152082 Hom.: 4306 Cov.: 33 AF XY: 0.238 AC XY: 17726 AN XY: 74346

African (AFR) AF: 0.239 AC: 9902 AN: 41484

American (AMR) AF: 0.202 AC: 3082 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.162 AC: 839 AN: 5176

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3172 AN: 10550

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15503 AN: 67996

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.228 Hom.: 5601

Bravo AF: 0.226

Asia WGS AF: 0.233 AC: 811 AN: 3476

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	-0.78
CADD	Benign	4.4
DANN	Benign	0.73
PhyloP100		-0.076
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: rs3735514; hg19: chr7-83631517; COSMIC: COSV54894059;