20-6765851-C-T

Variant names:

• chr20-6765851-C-T
• rs1980499
• ENST00000788333.1:n.634+1G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000788333.1(ENSG00000302641):​n.634+1G>A variant causes a splice donor, intron 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: ENSG00000302641 ENST00000788333.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85
• Publications: 14 publications found

Genes affected

ENSG00000302641 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. Cryptic splice site detected, with MaxEntScore 3.5, offset of 42, new splice context is: tggGTactt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• 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 rank	MANE	Protein	UniProt
LOC105372517	XR_937228.2	n.1118+1G>A		splice_donor_variant, intron_variant	Intron 2 of 2
LOC105372517	XR_937229.2	n.727+1G>A		splice_donor_variant, intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302641	ENST00000788333.1	n.634+1G>A		splice_donor_variant, intron_variant	Intron 3 of 3
ENSG00000302641	ENST00000788334.1	n.651+1G>A		splice_donor_variant, intron_variant	Intron 3 of 3
ENSG00000302641	ENST00000788335.1	n.761+1G>A		splice_donor_variant, intron_variant	Intron 3 of 3

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

African (AFR) AF: 0.822 AC: 34075 AN: 41470

American (AMR) AF: 0.561 AC: 8565 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2536 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3890 AN: 5170

South Asian (SAS) AF: 0.677 AC: 3266 AN: 4824

European-Finnish (FIN) AF: 0.508 AC: 5348 AN: 10522

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34944 AN: 67962

Other (OTH) AF: 0.638 AC: 1346 AN: 2110

Alfa AF: 0.544 Hom.: 45812

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
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs1980499; hg19: chr20-6746498;