3-123019460-A-G

Position:

• chr3-123019460-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.-39+8004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,092 control chromosomes in the GnomAD database, including 14,178 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 0.33 (14178 hom., cov: 32)
• Consequence: SEMA5B NM_001031702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5B	NM_001031702.4	c.-39+8004T>C		intron_variant		ENST00000357599.8	NP_001026872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5B	ENST00000357599.8	c.-39+8004T>C		intron_variant		1	NM_001031702.4	ENSP00000350215

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49966 AN: 151974 Hom.: 14121 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.329 AC: 50087 AN: 152092 Hom.: 14178 Cov.: 32 AF XY: 0.324 AC XY: 24067 AN XY: 74362

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.295

Alfa AF: 0.246 Hom.: 1073

Bravo AF: 0.357

Asia WGS AF: 0.348 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7632505; hg19: chr3-122738307;