21-17788803-G-C

Variant names:

• chr21-17788803-G-C
• rs243605
• ENST00000430401.5:n.34-1593C>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.34-1593C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,706 control chromosomes in the GnomAD database, including 17,580 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 (17580 hom., cov: 30)
• Consequence: C21orf91-OT1 ENST00000430401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 4 publications found

Genes affected

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

ENSG00000244676 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.*4612C>G		downstream_gene_variant		ENST00000284881.9	NP_001093890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.*4612C>G		downstream_gene_variant		2	NM_001100420.2	ENSP00000284881.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72850 AN: 151588 Hom.: 17560 Cov.: 30

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.481 AC: 72920 AN: 151706 Hom.: 17580 Cov.: 30 AF XY: 0.483 AC XY: 35793 AN XY: 74118

African (AFR) AF: 0.471 AC: 19472 AN: 41314

American (AMR) AF: 0.470 AC: 7162 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2659 AN: 5160

South Asian (SAS) AF: 0.554 AC: 2669 AN: 4816

European-Finnish (FIN) AF: 0.484 AC: 5061 AN: 10466

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

European-Non Finnish (NFE) AF: 0.477 AC: 32384 AN: 67926

Other (OTH) AF: 0.506 AC: 1070 AN: 2114

Alfa AF: 0.301 Hom.: 688

Bravo AF: 0.478

Asia WGS AF: 0.522 AC: 1814 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	6.5
DANN	Benign	0.44
PhyloP100		1.7

Splicing

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

Other links and lift over

dbSNP: rs243605; hg19: chr21-19161120;