ENST00000448879.5:c.-83+25252C>T

Variant names:

• chr7-84281955-G-A
• rs488333
• ENST00000448879.5:c.-83+25252C>T

Variant summary

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

The ENST00000448879.5(SEMA3A):​c.-83+25252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,046 control chromosomes in the GnomAD database, including 42,638 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 0.74 (42638 hom., cov: 32)
• Consequence: SEMA3A ENST00000448879.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	XM_005250110.4	c.-83+25252C>T		intron_variant	Intron 3 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.-83+13087C>T		intron_variant	Intron 4 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000448879.5	c.-83+25252C>T		intron_variant	Intron 4 of 4	5		ENSP00000402093.1
SEMA3A	ENST00000424555.5	c.-83+25252C>T		intron_variant	Intron 3 of 3	4		ENSP00000404800.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112903 AN: 151928 Hom.: 42594 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.743 AC: 112999 AN: 152046 Hom.: 42638 Cov.: 32 AF XY: 0.739 AC XY: 54931 AN XY: 74294

African (AFR) AF: 0.875 AC: 36311 AN: 41508

American (AMR) AF: 0.637 AC: 9722 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3472

East Asian (EAS) AF: 0.789 AC: 4060 AN: 5146

South Asian (SAS) AF: 0.671 AC: 3232 AN: 4820

European-Finnish (FIN) AF: 0.655 AC: 6916 AN: 10552

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48077 AN: 67968

Other (OTH) AF: 0.727 AC: 1536 AN: 2112

Alfa AF: 0.718 Hom.: 85426

Bravo AF: 0.745

Asia WGS AF: 0.756 AC: 2624 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.26
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs488333; hg19: chr7-83911271;