rs797820

Variant names:

• chr7-83979723-G-A
• rs797820
• NM_006080.3:c.1652+1598C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-83979723-G-A
• chr7-83979723-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006080.3(SEMA3A):​c.1652+1598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,110 control chromosomes in the GnomAD database, including 49,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (49213 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1652+1598C>T		intron_variant	Intron 14 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1652+1598C>T		intron_variant	Intron 17 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1652+1598C>T		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.1652+1598C>T		intron_variant	Intron 14 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1652+1598C>T		intron_variant	Intron 15 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121207 AN: 151990 Hom.: 49150 Cov.: 32

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.798 AC: 121332 AN: 152110 Hom.: 49213 Cov.: 32 AF XY: 0.790 AC XY: 58743 AN XY: 74354

African (AFR) AF: 0.945 AC: 39237 AN: 41538

American (AMR) AF: 0.768 AC: 11744 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2504 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4582 AN: 5174

South Asian (SAS) AF: 0.733 AC: 3533 AN: 4820

European-Finnish (FIN) AF: 0.648 AC: 6833 AN: 10540

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50305 AN: 67962

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.760 Hom.: 65743

Bravo AF: 0.817

Asia WGS AF: 0.837 AC: 2892 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.75
PhyloP100		-0.23
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: rs797820; hg19: chr7-83609039;