21-17789198-A-G

Variant names:

• chr21-17789198-A-G
• rs243607
• NM_001100420.2:c.*4217T>C

Variant summary

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

The NM_001100420.2(C21orf91):​c.*4217T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.479 in 151,598 control chromosomes in the GnomAD database, including 17,476 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 (17476 hom., cov: 30)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• 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]

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

ENSG00000244676 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	NM_001100420.2	MANE Select	c.*4217T>C		3_prime_UTR	Exon 5 of 5	NP_001093890.1
	C21orf91	NM_017447.4		c.*4217T>C		3_prime_UTR	Exon 5 of 5	NP_059143.3
	C21orf91	NM_001100421.2		c.*4382T>C		3_prime_UTR	Exon 4 of 4	NP_001093891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	ENST00000284881.9	TSL:2 MANE Select	c.*4217T>C		3_prime_UTR	Exon 5 of 5	ENSP00000284881.4
	C21orf91-OT1	ENST00000430401.5	TSL:1	n.34-1988T>C		intron	N/A
	C21orf91-OT1	ENST00000439392.1	TSL:1	n.34-1988T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72571 AN: 151478 Hom.: 17456 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.502

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.479 AC: 72641 AN: 151596 Hom.: 17476 Cov.: 30 AF XY: 0.481 AC XY: 35651 AN XY: 74048

African (AFR) AF: 0.468 AC: 19309 AN: 41300

American (AMR) AF: 0.469 AC: 7139 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3464

East Asian (EAS) AF: 0.515 AC: 2660 AN: 5162

South Asian (SAS) AF: 0.554 AC: 2666 AN: 4810

European-Finnish (FIN) AF: 0.482 AC: 5053 AN: 10476

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32310 AN: 67862

Other (OTH) AF: 0.506 AC: 1065 AN: 2106

Alfa AF: 0.476 Hom.: 22078

Bravo AF: 0.477

Asia WGS AF: 0.521 AC: 1809 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs243607; hg19: chr21-19161515;