rs2258119

Positions:

• chr21-17795162-T-C

Variant summary

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

The NM_001100420.2(C21orf91):​c.727+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,207,152 control chromosomes in the GnomAD database, including 31,384 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 0.24 (4688 hom., cov: 32)
  • Exomes 𝑓: 0.22 (26696 hom.)
• Consequence: C21orf91 NM_001100420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

Genes affected

C21orf91 (HGNC:16459): (chromosome 21 open reading frame 91) Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.727+46A>G		intron_variant		ENST00000284881.9	NP_001093890.1
LOC124900465	XR_007067823.1	n.1605+38373T>C		intron_variant, non_coding_transcript_variant
C21orf91	NM_001100421.2	c.664+1420A>G		intron_variant			NP_001093891.1
C21orf91	NM_017447.4	c.727+46A>G		intron_variant			NP_059143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.727+46A>G		intron_variant		2	NM_001100420.2	ENSP00000284881	P4
	ENST00000428689.5	n.71+1604T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36251 AN: 152008 Hom.: 4685 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.225 AC: 55821 AN: 247768 Hom.: 6957 AF XY: 0.218 AC XY: 29294 AN XY: 134580

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.396

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.218 AC: 229990 AN: 1055026 Hom.: 26696 Cov.: 14 AF XY: 0.214 AC XY: 116676 AN XY: 544078

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.238 AC: 36262 AN: 152126 Hom.: 4688 Cov.: 32 AF XY: 0.234 AC XY: 17430 AN XY: 74378

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.195

Alfa AF: 0.211 Hom.: 3834

Bravo AF: 0.254

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2258119; hg19: chr21-19167479; COSMIC: COSV53033394; COSMIC: COSV53033394;