3-122911476-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001031702.4(SEMA5B):c.3091+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,601,644 control chromosomes in the GnomAD database, including 503,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (40081 hom., cov: 33)
  • Exomes 𝑓: 0.79 (463643 hom.)
• Consequence: SEMA5B NM_001031702.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-122911476-T-G is Benign according to our data. Variant chr3-122911476-T-G is described in ClinVar as [Benign]. Clinvar id is 1224885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5B	NM_001031702.4	c.3091+15A>C		intron_variant		ENST00000357599.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5B	ENST00000357599.8	c.3091+15A>C		intron_variant		1	NM_001031702.4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108405 AN: 151666 Hom.: 40068 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.742

GnomAD3 exomes AF: 0.706 AC: 162081 AN: 229678 Hom.: 60019 AF XY: 0.720 AC XY: 88697 AN XY: 123274

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.780

Gnomad EAS exome AF: 0.328

Gnomad SAS exome AF: 0.729

Gnomad FIN exome AF: 0.727

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.748

GnomAD4 exome AF: 0.792 AC: 1147875 AN: 1449860 Hom.: 463643 Cov.: 50 AF XY: 0.791 AC XY: 569593 AN XY: 719724

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.526

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.834

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.715 AC: 108458 AN: 151784 Hom.: 40081 Cov.: 33 AF XY: 0.708 AC XY: 52518 AN XY: 74142

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.743

Alfa AF: 0.804 Hom.: 84172

Bravo AF: 0.696

Asia WGS AF: 0.588 AC: 2048 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.3
Dann	Benign	0.13

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: rs2303982; hg19: chr3-122630323; COSMIC: COSV52094182;