5-116555387-A-G

Position:

• chr5-116555387-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020796.5(SEMA6A):​c.-39+18798T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,106 control chromosomes in the GnomAD database, including 21,003 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 0.50 (21003 hom., cov: 33)
• Consequence: SEMA6A NM_020796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

Genes affected

SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA6A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6A	NM_020796.5	c.-39+18798T>C		intron_variant		ENST00000343348.11	NP_065847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6A	ENST00000343348.11	c.-39+18798T>C		intron_variant		1	NM_020796.5	ENSP00000345512.6
SEMA6A	ENST00000257414.12	c.-39+18798T>C		intron_variant		1		ENSP00000257414.8
SEMA6A	ENST00000512156.1	n.51-4741T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75327 AN: 151984 Hom.: 20988 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.496 AC: 75374 AN: 152106 Hom.: 21003 Cov.: 33 AF XY: 0.497 AC XY: 36948 AN XY: 74370

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.557

Alfa AF: 0.593 Hom.: 29887

Bravo AF: 0.480

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.2
DANN	Benign	0.48

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: rs254079; hg19: chr5-115891083;