rs701320

Variant names:

• chr7-83977202-G-A
• rs701320
• NM_006080.3:c.1653-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-83977202-G-A
• chr7-83977202-G-C
• chr7-83977202-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_006080.3(SEMA3A):​c.1653-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,552,192 control chromosomes in the GnomAD database, including 485,009 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52439 hom., cov: 31)
  • Exomes 𝑓: 0.78 (432570 hom.)
• Consequence: SEMA3A NM_006080.3 splice_region, intron
• Scores: Splicing: ADA: 0.00007299
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.46
• Publications: 18 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-83977202-G-A is Benign according to our data. Variant chr7-83977202-G-A is described in ClinVar as Benign. ClinVar VariationId is 1174901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1653-6C>T		splice_region_variant, intron_variant	Intron 14 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1653-6C>T		splice_region_variant, intron_variant	Intron 17 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1653-6C>T		splice_region_variant, intron_variant	Intron 18 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1653-6C>T		splice_region_variant, intron_variant	Intron 14 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1653-6C>T		splice_region_variant, intron_variant	Intron 15 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125272 AN: 151856 Hom.: 52367 Cov.: 31

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.827

GnomAD2 exomes AF: 0.788 AC: 186776 AN: 236956 AF XY: 0.780

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 0.898

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.773

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.784 AC: 1098096 AN: 1400220 Hom.: 432570 Cov.: 23 AF XY: 0.783 AC XY: 546392 AN XY: 697954

African (AFR) AF: 0.964 AC: 30572 AN: 31726

American (AMR) AF: 0.828 AC: 34801 AN: 42048

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 19565 AN: 25128

East Asian (EAS) AF: 0.890 AC: 33752 AN: 37938

South Asian (SAS) AF: 0.742 AC: 58717 AN: 79178

European-Finnish (FIN) AF: 0.675 AC: 35080 AN: 51960

Middle Eastern (MID) AF: 0.723 AC: 4059 AN: 5612

European-Non Finnish (NFE) AF: 0.782 AC: 835928 AN: 1068732

Other (OTH) AF: 0.788 AC: 45622 AN: 57898

GnomAD4 genome AF: 0.825 AC: 125406 AN: 151972 Hom.: 52439 Cov.: 31 AF XY: 0.817 AC XY: 60700 AN XY: 74278

African (AFR) AF: 0.960 AC: 39850 AN: 41512

American (AMR) AF: 0.800 AC: 12214 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4575 AN: 5156

South Asian (SAS) AF: 0.757 AC: 3653 AN: 4824

European-Finnish (FIN) AF: 0.672 AC: 7058 AN: 10502

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52670 AN: 67928

Other (OTH) AF: 0.830 AC: 1751 AN: 2110

Alfa AF: 0.789 Hom.: 155386

Bravo AF: 0.843

Asia WGS AF: 0.851 AC: 2957 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		2.5
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.052
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: rs701320; hg19: chr7-83606518;