rs4378918

Positions:

• chr3-122920162-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.1688+1753T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,094 control chromosomes in the GnomAD database, including 23,411 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 0.53 (23411 hom., cov: 32)
• Consequence: SEMA5B NM_001031702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5B	NM_001031702.4	c.1688+1753T>C		intron_variant		ENST00000357599.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5B	ENST00000357599.8	c.1688+1753T>C		intron_variant		1	NM_001031702.4

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80083 AN: 151976 Hom.: 23411 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.527 AC: 80089 AN: 152094 Hom.: 23411 Cov.: 32 AF XY: 0.524 AC XY: 38927 AN XY: 74338

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.528

Alfa AF: 0.635 Hom.: 16635

Bravo AF: 0.500

Asia WGS AF: 0.469 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.60

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: rs4378918; hg19: chr3-122639009; COSMIC: COSV52106980;