rs3735513

Variant names:

• chr7-84002060-T-C
• rs3735513
• NM_006080.3:c.1361-14A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-84002060-T-C
• chr7-84002060-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006080.3(SEMA3A):​c.1361-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,509,330 control chromosomes in the GnomAD database, including 42,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4460 hom., cov: 33)
  • Exomes 𝑓: 0.24 (38394 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-84002060-T-C is Benign according to our data. Variant chr7-84002060-T-C is described in ClinVar as Benign. ClinVar VariationId is 1601502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.1361-14A>G		intron_variant	Intron 11 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1361-14A>G		intron_variant	Intron 14 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1361-14A>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.1361-14A>G		intron_variant	Intron 11 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1361-14A>G		intron_variant	Intron 12 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36236 AN: 151930 Hom.: 4461 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.237 AC: 58101 AN: 244654 AF XY: 0.245

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.151

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.236 AC: 320433 AN: 1357282 Hom.: 38394 Cov.: 20 AF XY: 0.239 AC XY: 162659 AN XY: 681322

African (AFR) AF: 0.249 AC: 7776 AN: 31178

American (AMR) AF: 0.175 AC: 7519 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6201 AN: 25232

East Asian (EAS) AF: 0.168 AC: 6503 AN: 38810

South Asian (SAS) AF: 0.321 AC: 26788 AN: 83332

European-Finnish (FIN) AF: 0.303 AC: 16075 AN: 53098

Middle Eastern (MID) AF: 0.333 AC: 1859 AN: 5580

European-Non Finnish (NFE) AF: 0.229 AC: 234043 AN: 1020210

Other (OTH) AF: 0.241 AC: 13669 AN: 56784

GnomAD4 genome AF: 0.238 AC: 36249 AN: 152048 Hom.: 4460 Cov.: 33 AF XY: 0.242 AC XY: 17988 AN XY: 74334

African (AFR) AF: 0.250 AC: 10361 AN: 41484

American (AMR) AF: 0.203 AC: 3104 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.162 AC: 835 AN: 5158

South Asian (SAS) AF: 0.314 AC: 1514 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3185 AN: 10560

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

European-Non Finnish (NFE) AF: 0.229 AC: 15583 AN: 67960

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.238 Hom.: 2926

Bravo AF: 0.230

Asia WGS AF: 0.237 AC: 827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.31
DANN	Benign	0.66
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3735513; hg19: chr7-83631376; COSMIC: COSV54864780;