chr22-50278700-T-G

Variant names:

• chr22-50278700-T-G
• rs28718510
• ENST00000479818.5:n.141A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012401.4(PLXNB2):​c.4547-4A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,606,100 control chromosomes in the GnomAD database, including 265,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20305 hom., cov: 33)
  • Exomes 𝑓: 0.58 (245152 hom.)
• Consequence: PLXNB2 NM_012401.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008622
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.998
• Publications: 14 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-50278700-T-G is Benign according to our data. Variant chr22-50278700-T-G is described in ClinVar as [Benign]. Clinvar id is 1676933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4	c.4547-4A>C		splice_region_variant, intron_variant	Intron 28 of 36	ENST00000359337.9	NP_036533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9	c.4547-4A>C		splice_region_variant, intron_variant	Intron 28 of 36	5	NM_012401.4	ENSP00000352288.4

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77003 AN: 151984 Hom.: 20293 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.525

GnomAD2 exomes AF: 0.558 AC: 131756 AN: 236020 AF XY: 0.567

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.579

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.578 AC: 840634 AN: 1453998 Hom.: 245152 Cov.: 39 AF XY: 0.580 AC XY: 419285 AN XY: 723160

African (AFR) AF: 0.341 AC: 11381 AN: 33340

American (AMR) AF: 0.494 AC: 21753 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 12923 AN: 26036

East Asian (EAS) AF: 0.576 AC: 22688 AN: 39388

South Asian (SAS) AF: 0.642 AC: 54965 AN: 85608

European-Finnish (FIN) AF: 0.565 AC: 28735 AN: 50886

Middle Eastern (MID) AF: 0.507 AC: 2902 AN: 5722

European-Non Finnish (NFE) AF: 0.587 AC: 651275 AN: 1108948

Other (OTH) AF: 0.566 AC: 34012 AN: 60050

GnomAD4 genome AF: 0.506 AC: 77022 AN: 152102 Hom.: 20305 Cov.: 33 AF XY: 0.508 AC XY: 37797 AN XY: 74346

African (AFR) AF: 0.343 AC: 14245 AN: 41492

American (AMR) AF: 0.521 AC: 7966 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3189 AN: 5156

South Asian (SAS) AF: 0.652 AC: 3150 AN: 4828

European-Finnish (FIN) AF: 0.563 AC: 5967 AN: 10594

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39107 AN: 67954

Other (OTH) AF: 0.528 AC: 1114 AN: 2110

Alfa AF: 0.531 Hom.: 11864

Bravo AF: 0.492

Asia WGS AF: 0.562 AC: 1951 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 16, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs28718510; hg19: chr22-50717129; COSMIC: COSV63781900; COSMIC: COSV63781900;