20-6765851-C-T

Position:

• chr20-6765851-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The XR_937229.2(LOC105372517):​n.727+1G>A variant causes a splice donor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,992 control chromosomes in the GnomAD database, including 31,068 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 0.62 (31068 hom., cov: 32)
• Consequence: LOC105372517 XR_937229.2 splice_donor, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85

Genes affected

LOC105372517 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105372517	XR_937229.2	n.727+1G>A		splice_donor_variant, non_coding_transcript_variant
LOC105372517	XR_937228.2	n.1118+1G>A		splice_donor_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94583 AN: 151874 Hom.: 31017 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.623 AC: 94687 AN: 151992 Hom.: 31068 Cov.: 32 AF XY: 0.623 AC XY: 46247 AN XY: 74260

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.638

Alfa AF: 0.538 Hom.: 31072

Bravo AF: 0.633

Asia WGS AF: 0.739 AC: 2572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1980499; hg19: chr20-6746498;