1-156153439-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000355014.6(SEMA4A):c.-29-1111C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,122 control chromosomes in the GnomAD database, including 5,834 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 0.26 (5832 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: SEMA4A ENST00000355014.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

SEMA4A (HGNC:10729): (semaphorin 4A) This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA4A	NM_001193300.2	c.-254-92C>G		intron_variant
SEMA4A	NM_001193301.2	c.-29-1111C>G		intron_variant
SEMA4A	NM_001370568.1	c.-158-2975C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA4A	ENST00000355014.6	c.-29-1111C>G		intron_variant		1		P1
SEMA4A	ENST00000633494.1	c.-67C>G		5_prime_UTR_variant	2/4	4
SEMA4A	ENST00000414683.5	c.-158-2975C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39457 AN: 151950 Hom.: 5806 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.222 AC: 12 AN: 54 Hom.: 2 Cov.: 0 AF XY: 0.192 AC XY: 5 AN XY: 26

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.260 AC: 39534 AN: 152068 Hom.: 5832 Cov.: 32 AF XY: 0.258 AC XY: 19183 AN XY: 74350

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.241

Alfa AF: 0.102 Hom.: 139

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.0
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs3738582; hg19: chr1-156123230; COSMIC: COSV61773875; COSMIC: COSV61773875;