7-84134993-C-G

Variant names:

• chr7-84134993-C-G
• rs17241389
• NM_006080.3:c.113-42G>C

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.113-42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,558,342 control chromosomes in the GnomAD database, including 241,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20105 hom., cov: 32)
  • Exomes 𝑓: 0.56 (221638 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• 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=-0.82).
• BP6: Variant 7-84134993-C-G is Benign according to our data. Variant chr7-84134993-C-G is described in ClinVar as Benign. ClinVar VariationId is 1266731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	NM_006080.3	MANE Select	c.113-42G>C		intron	N/A	NP_006071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.113-42G>C		intron	N/A	ENSP00000265362.3
	SEMA3A	ENST00000436949.5	TSL:5	c.113-42G>C		intron	N/A	ENSP00000415260.1
	SEMA3A	ENST00000420047.1	TSL:4	c.113-42G>C		intron	N/A	ENSP00000391900.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76887 AN: 151836 Hom.: 20098 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.540 AC: 127271 AN: 235612 AF XY: 0.537

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.696

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.559

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.558 AC: 784976 AN: 1406388 Hom.: 221638 Cov.: 22 AF XY: 0.556 AC XY: 389785 AN XY: 701030

African (AFR) AF: 0.357 AC: 11532 AN: 32276

American (AMR) AF: 0.561 AC: 24155 AN: 43040

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 13928 AN: 24456

East Asian (EAS) AF: 0.706 AC: 27767 AN: 39340

South Asian (SAS) AF: 0.438 AC: 35787 AN: 81736

European-Finnish (FIN) AF: 0.526 AC: 27604 AN: 52512

Middle Eastern (MID) AF: 0.502 AC: 2794 AN: 5562

European-Non Finnish (NFE) AF: 0.570 AC: 608853 AN: 1069012

Other (OTH) AF: 0.557 AC: 32556 AN: 58454

GnomAD4 genome AF: 0.506 AC: 76910 AN: 151954 Hom.: 20105 Cov.: 32 AF XY: 0.506 AC XY: 37600 AN XY: 74274

African (AFR) AF: 0.364 AC: 15077 AN: 41410

American (AMR) AF: 0.563 AC: 8592 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3538 AN: 5160

South Asian (SAS) AF: 0.437 AC: 2109 AN: 4822

European-Finnish (FIN) AF: 0.533 AC: 5614 AN: 10538

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38242 AN: 67978

Other (OTH) AF: 0.540 AC: 1142 AN: 2114

Alfa AF: 0.541 Hom.: 4103

Bravo AF: 0.507

Asia WGS AF: 0.529 AC: 1835 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-1.2
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: rs17241389; hg19: chr7-83764309;