rs4378918

Variant names:

• chr3-122920162-A-G
• rs4378918
• NM_001031702.4:c.1688+1753T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031702.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5B	NM_001031702.4	MANE Select	c.1688+1753T>C		intron	N/A	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.1850+1753T>C		intron	N/A	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.1760+1753T>C		intron	N/A	NP_001424492.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5B	ENST00000357599.8	TSL:1 MANE Select	c.1688+1753T>C		intron	N/A	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.1850+1753T>C		intron	N/A	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.1688+1753T>C		intron	N/A	ENSP00000479602.1	Q9P283-1

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

African (AFR) AF: 0.301 AC: 12486 AN: 41490

American (AMR) AF: 0.447 AC: 6836 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5160

South Asian (SAS) AF: 0.601 AC: 2899 AN: 4820

European-Finnish (FIN) AF: 0.639 AC: 6757 AN: 10572

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45560 AN: 67980

Other (OTH) AF: 0.528 AC: 1115 AN: 2110

Alfa AF: 0.634 Hom.: 18317

Bravo AF: 0.500

Asia WGS AF: 0.469 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4378918;

hg19: chr3-122639009;

COSMIC: COSV52106980;