21-46302477-A-G

Position:

• chr21-46302477-A-G

Variant summary

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

The NM_058180.5(C21orf58):​c.813+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,596,832 control chromosomes in the GnomAD database, including 373,867 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29835 hom., cov: 32)
  • Exomes 𝑓: 0.69 (344032 hom.)
• Consequence: C21orf58 NM_058180.5 splice_region, intron
• Scores: Splicing: ADA: 0.000007724
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

C21orf58 (HGNC:1300): (chromosome 21 open reading frame 58)

YBEY (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C21orf58	NM_058180.5	c.813+8T>C		splice_region_variant, intron_variant		ENST00000291691.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C21orf58	ENST00000291691.12	c.813+8T>C		splice_region_variant, intron_variant		2	NM_058180.5	A2

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93087 AN: 151804 Hom.: 29820 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.654 AC: 152655 AN: 233452 Hom.: 51035 AF XY: 0.654 AC XY: 82926 AN XY: 126722

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.711

Gnomad ASJ exome AF: 0.680

Gnomad EAS exome AF: 0.443

Gnomad SAS exome AF: 0.608

Gnomad FIN exome AF: 0.714

Gnomad NFE exome AF: 0.704

Gnomad OTH exome AF: 0.690

GnomAD4 exome AF: 0.686 AC: 990578 AN: 1444910 Hom.: 344032 Cov.: 30 AF XY: 0.683 AC XY: 490951 AN XY: 718576

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.613

Gnomad4 FIN exome AF: 0.718

Gnomad4 NFE exome AF: 0.710

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.613 AC: 93142 AN: 151922 Hom.: 29835 Cov.: 32 AF XY: 0.612 AC XY: 45439 AN XY: 74224

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.615

Alfa AF: 0.676 Hom.: 29371

Bravo AF: 0.601

Asia WGS AF: 0.523 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.15
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000077
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs1556337; hg19: chr21-47722391; COSMIC: COSV52448887; COSMIC: COSV52448887;