rs3738581

Positions:

• chr1-156177767-C-T

Variant summary

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

The 1-156177767-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,758 control chromosomes in the GnomAD database, including 18,040 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 0.47 (17970 hom., cov: 30)
  • Exomes 𝑓: 0.38 (70 hom.)
• Consequence: SEMA4A NM_022367.4 downstream_gene
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4A	NM_022367.4			downstream_gene_variant		ENST00000368285.8	NP_071762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4A	ENST00000368285.8			downstream_gene_variant		1	NM_022367.4	ENSP00000357268	P1
SEMA4A	ENST00000355014.6			downstream_gene_variant		1		ENSP00000347117	P1
SEMA4A	ENST00000368282.1			downstream_gene_variant		1		ENSP00000357265	P1
SEMA4A	ENST00000368284.5			downstream_gene_variant		2		ENSP00000357267

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71188 AN: 151786 Hom.: 17929 Cov.: 30

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.382 AC: 326 AN: 854 Hom.: 70 Cov.: 0 AF XY: 0.397 AC XY: 201 AN XY: 506

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.469 AC: 71277 AN: 151904 Hom.: 17970 Cov.: 30 AF XY: 0.464 AC XY: 34413 AN XY: 74210

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.439

Alfa AF: 0.421 Hom.: 23271

Bravo AF: 0.475

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3738581; hg19: chr1-156147558;