rs2824483

Positions:

• chr21-17767458-T-C
• chr21-17767458-T-A

Variant summary

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

The ENST00000430815.5(C21orf91-OT1):​n.343+128A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,996 control chromosomes in the GnomAD database, including 12,051 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 0.39 (12051 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: C21orf91-OT1 ENST00000430815.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

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

LOC124900465 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900465	XR_007067823.1	n.1605+10669T>C		intron_variant, non_coding_transcript_variant
LOC124900465	XR_007067822.1	n.1605+10669T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91-OT1	ENST00000430815.5	n.343+128A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58685 AN: 151876 Hom.: 12033 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.386 AC: 58739 AN: 151994 Hom.: 12051 Cov.: 32 AF XY: 0.386 AC XY: 28652 AN XY: 74302

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.415

Alfa AF: 0.331 Hom.: 18046

Bravo AF: 0.407

Asia WGS AF: 0.440 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2824483; hg19: chr21-19139775;