6-12288986-T-G

Position:

• chr6-12288986-T-G

Variant summary

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

The NM_001416564.1(EDN1):​c.-2+912T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,004 control chromosomes in the GnomAD database, including 5,109 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 0.24 (5109 hom., cov: 32)
• Consequence: EDN1 NM_001416564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

EDN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001416564.1	c.-2+912T>G		intron_variant
EDN1	NM_001416565.1	c.-1-1643T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36414 AN: 151886 Hom.: 5100 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.240 AC: 36456 AN: 152004 Hom.: 5109 Cov.: 32 AF XY: 0.242 AC XY: 18003 AN XY: 74282

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.211

Alfa AF: 0.236 Hom.: 708

Bravo AF: 0.238

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1800541; hg19: chr6-12289219;