rs7809708

Variant names:

• chr7-83963175-T-C
• rs7809708
• NM_006080.3:c.1860+30A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-83963175-T-C
• chr7-83963175-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.1860+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,606,842 control chromosomes in the GnomAD database, including 54,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5528 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48628 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.162
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-83963175-T-C is Benign according to our data. Variant chr7-83963175-T-C is described in ClinVar as [Benign]. Clinvar id is 1292758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1860+30A>G		intron_variant	Intron 16 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1860+30A>G		intron_variant	Intron 19 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1860+30A>G		intron_variant	Intron 20 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1860+30A>G		intron_variant	Intron 16 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1860+30A>G		intron_variant	Intron 17 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40120 AN: 152000 Hom.: 5527 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.225 AC: 56125 AN: 249096 AF XY: 0.227

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.0452

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.253 AC: 367587 AN: 1454724 Hom.: 48628 Cov.: 30 AF XY: 0.252 AC XY: 182512 AN XY: 724116

African (AFR) AF: 0.320 AC: 10701 AN: 33402

American (AMR) AF: 0.159 AC: 7109 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5865 AN: 26094

East Asian (EAS) AF: 0.0312 AC: 1237 AN: 39674

South Asian (SAS) AF: 0.176 AC: 15203 AN: 86178

European-Finnish (FIN) AF: 0.262 AC: 13159 AN: 50222

Middle Eastern (MID) AF: 0.328 AC: 1885 AN: 5750

European-Non Finnish (NFE) AF: 0.268 AC: 297465 AN: 1108514

Other (OTH) AF: 0.249 AC: 14963 AN: 60206

GnomAD4 genome AF: 0.264 AC: 40142 AN: 152118 Hom.: 5528 Cov.: 32 AF XY: 0.261 AC XY: 19401 AN XY: 74358

African (AFR) AF: 0.311 AC: 12888 AN: 41494

American (AMR) AF: 0.213 AC: 3248 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3466

East Asian (EAS) AF: 0.0427 AC: 221 AN: 5176

South Asian (SAS) AF: 0.170 AC: 820 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2866 AN: 10570

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18289 AN: 67994

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.263 Hom.: 1045

Bravo AF: 0.263

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 09, 2018

GeneDx

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	-0.79
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7809708; hg19: chr7-83592491; COSMIC: COSV54864733;