rs13094003

chr3-122961294-A-G

Variant summary

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

The NM_001031702.4(SEMA5B):c.-31T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,324 control chromosomes in the GnomAD database, including 42,009 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 0.24 (4382 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37627 hom.)
• Consequence: SEMA5B NM_001031702.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5B	NM_001031702.4	c.-31T>C		5_prime_UTR_variant	2/23	ENST00000357599.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5B	ENST00000357599.8	c.-31T>C		5_prime_UTR_variant	2/23	1	NM_001031702.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35925 AN: 151974 Hom.: 4376 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.244 AC: 60934 AN: 249638 Hom.: 7793 AF XY: 0.239 AC XY: 32317 AN XY: 134978

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.389

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.224 AC: 327562 AN: 1460232 Hom.: 37627 Cov.: 33 AF XY: 0.223 AC XY: 162167 AN XY: 726428

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.236 AC: 35949 AN: 152092 Hom.: 4382 Cov.: 32 AF XY: 0.243 AC XY: 18035 AN XY: 74330

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.233

Alfa AF: 0.220 Hom.: 7552

Bravo AF: 0.238

Asia WGS AF: 0.244 AC: 848 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.2
Dann	Benign	0.66

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: rs13094003; hg19: chr3-122680141; COSMIC: COSV52091520;