chr21-17792594-C-T

Variant names:

• chr21-17792594-C-T
• rs2220511
• NM_001100420.2:c.*821G>A

Variant summary

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

The NM_001100420.2(C21orf91):​c.*821G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,896 control chromosomes in the GnomAD database, including 9,337 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 0.34 (9337 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 10 publications found

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]

ENSG00000244676 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100420.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	NM_001100420.2	MANE Select	c.*821G>A		3_prime_UTR	Exon 5 of 5	NP_001093890.1
	C21orf91	NM_017447.4		c.*821G>A		3_prime_UTR	Exon 5 of 5	NP_059143.3
	C21orf91	NM_001100421.2		c.*986G>A		3_prime_UTR	Exon 4 of 4	NP_001093891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	ENST00000284881.9	TSL:2 MANE Select	c.*821G>A		3_prime_UTR	Exon 5 of 5	ENSP00000284881.4	Q9NYK6-1
	ENSG00000244676	ENST00000813924.1		n.192-17901C>T		intron	N/A
	C21orf91-OT1	ENST00000430401.5	TSL:1	n.-85G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50882 AN: 151778 Hom.: 9324 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.286

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.335 AC: 50936 AN: 151896 Hom.: 9337 Cov.: 32 AF XY: 0.331 AC XY: 24568 AN XY: 74224

African (AFR) AF: 0.483 AC: 20004 AN: 41410

American (AMR) AF: 0.358 AC: 5463 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2183 AN: 5166

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2152 AN: 10554

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18354 AN: 67910

Other (OTH) AF: 0.283 AC: 596 AN: 2106

Alfa AF: 0.288 Hom.: 11147

Bravo AF: 0.356

Asia WGS AF: 0.357 AC: 1241 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.49
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2220511; hg19: chr21-19164911;