21-17782249-T-C

Variant names:

• chr21-17782249-T-C
• rs243588
• ENST00000430401.5:n.217-4630A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000430401.5(C21orf91-OT1):​n.217-4630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,014 control chromosomes in the GnomAD database, including 17,570 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 0.48 (17570 hom., cov: 32)
• Consequence: C21orf91-OT1 ENST00000430401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 7 publications found

Genes affected

C21orf91-OT1 (HGNC:16729): (C21orf91 overlapping transcript 1)

ENSG00000244676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900465	XR_007067822.1	n.2480T>C		non_coding_transcript_exon_variant	Exon 3 of 3
C21orf91-OT1	NR_038870.1	n.217-4630A>G		intron_variant	Intron 2 of 2
C21orf91-OT1	NR_038871.1	n.281+3299A>G		intron_variant	Intron 3 of 3
LOC124900465	XR_007067823.1	n.1605+25460T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91-OT1	ENST00000430401.5	n.217-4630A>G		intron_variant	Intron 2 of 2	1
C21orf91-OT1	ENST00000439392.1	n.281+3299A>G		intron_variant	Intron 3 of 3	1
ENSG00000244676	ENST00000813936.1	n.943T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72769 AN: 151896 Hom.: 17549 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.479 AC: 72841 AN: 152014 Hom.: 17570 Cov.: 32 AF XY: 0.483 AC XY: 35872 AN XY: 74276

African (AFR) AF: 0.447 AC: 18548 AN: 41456

American (AMR) AF: 0.471 AC: 7198 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1756 AN: 3462

East Asian (EAS) AF: 0.530 AC: 2741 AN: 5174

South Asian (SAS) AF: 0.560 AC: 2697 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5451 AN: 10550

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32688 AN: 67956

Other (OTH) AF: 0.507 AC: 1072 AN: 2114

Alfa AF: 0.477 Hom.: 8898

Bravo AF: 0.474

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs243588; hg19: chr21-19154566;