rs9868873

Variant names:

• chr3-123012063-G-A
• rs9868873
• NM_001031702.4:c.-39+15401C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031702.4(SEMA5B):​c.-39+15401C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,120 control chromosomes in the GnomAD database, including 11,168 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 0.28 (11168 hom., cov: 32)
• Consequence: SEMA5B NM_001031702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5B	NM_001031702.4	c.-39+15401C>T		intron_variant	Intron 1 of 22	ENST00000357599.8	NP_001026872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5B	ENST00000357599.8	c.-39+15401C>T		intron_variant	Intron 1 of 22	1	NM_001031702.4	ENSP00000350215.3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41942 AN: 152002 Hom.: 11119 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.276 AC: 42058 AN: 152120 Hom.: 11168 Cov.: 32 AF XY: 0.270 AC XY: 20052 AN XY: 74352

African (AFR) AF: 0.700 AC: 29050 AN: 41474

American (AMR) AF: 0.178 AC: 2721 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1076 AN: 5158

South Asian (SAS) AF: 0.195 AC: 943 AN: 4824

European-Finnish (FIN) AF: 0.0546 AC: 578 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0998 AC: 6785 AN: 67996

Other (OTH) AF: 0.228 AC: 483 AN: 2114

Alfa AF: 0.211 Hom.: 7642

Bravo AF: 0.305

Asia WGS AF: 0.312 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9868873; hg19: chr3-122730910;