rs375985220

Variant names:

• chr22-50278662-C-G
• rs375985220
• NM_012401.4:c.4581G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-50278662-C-G
• chr22-50278662-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012401.4(PLXNB2):​c.4581G>C​(p.Ser1527Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1527S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLXNB2 NM_012401.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 0 publications found

Genes affected

PLXNB2 (HGNC:9104): (plexin B2) Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06926319).
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4	c.4581G>C	p.Ser1527Ser	synonymous_variant	Exon 29 of 37	ENST00000359337.9	NP_036533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9	c.4581G>C	p.Ser1527Ser	synonymous_variant	Exon 29 of 37	5	NM_012401.4	ENSP00000352288.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245734 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460328 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726454

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.036
DANN	Benign	0.44
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.72	T
PhyloP100		-2.5
Sift4G	Benign	0.53	T
MVP		0.35
ClinPred		0.036	T
GERP RS		-9.2

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

Other links and lift over

dbSNP: rs375985220; hg19: chr22-50717091;