rs243607

Positions:

• chr21-17789198-A-G
• chr21-17789198-A-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.*4217T>C		3_prime_UTR_variant	5/5	ENST00000284881.9	NP_001093890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881	c.*4217T>C		3_prime_UTR_variant	5/5	2	NM_001100420.2	ENSP00000284881.4
C21orf91-OT1	ENST00000430401.5	n.34-1988T>C		intron_variant		1
C21orf91-OT1	ENST00000439392.1	n.34-1988T>C		intron_variant		1
C21orf91-OT1	ENST00000430815.5	n.48-1988T>C		intron_variant		5

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

Gnomad4 NFE exome AF: 0.500

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

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.506

Alfa AF: 0.475 Hom.: 16697

Bravo AF: 0.477

Asia WGS AF: 0.521 AC: 1809 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs243607; hg19: chr21-19161515;