rs510441

Positions:

• chr1-156160177-A-G

Variant summary

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

The NM_022367.4(SEMA4A):​c.569-266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,964 control chromosomes in the GnomAD database, including 3,276 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 0.20 (3276 hom., cov: 29)
• Consequence: SEMA4A NM_022367.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4A	NM_022367.4	c.569-266A>G		intron_variant		ENST00000368285.8	NP_071762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4A	ENST00000368285.8	c.569-266A>G		intron_variant		1	NM_022367.4	ENSP00000357268	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30216 AN: 151846 Hom.: 3278 Cov.: 29

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.199 AC: 30213 AN: 151964 Hom.: 3276 Cov.: 29 AF XY: 0.195 AC XY: 14500 AN XY: 74266

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.217

Alfa AF: 0.233 Hom.: 5621

Bravo AF: 0.193

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs510441; hg19: chr1-156129968;