5-116555387-A-G

Variant names:

• chr5-116555387-A-G
• rs254079
• NM_020796.5:c.-39+18798T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SEMA6A	NM_020796.5	c.-39+18798T>C		intron_variant	Intron 1 of 18	ENST00000343348.11	NP_065847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6A	ENST00000343348.11	c.-39+18798T>C		intron_variant	Intron 1 of 18	1	NM_020796.5	ENSP00000345512.6
SEMA6A	ENST00000257414.12	c.-39+18798T>C		intron_variant	Intron 1 of 19	1		ENSP00000257414.8
SEMA6A	ENST00000512156.1	n.51-4741T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.218 AC: 9062 AN: 41500

American (AMR) AF: 0.544 AC: 8313 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2364 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2907 AN: 5174

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6401 AN: 10554

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42066 AN: 67992

Other (OTH) AF: 0.557 AC: 1176 AN: 2112

Alfa AF: 0.582 Hom.: 42479

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
PhyloP100		0.29
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs254079; hg19: chr5-115891083;