rs2824499

Positions:

• chr21-17806954-C-T
• chr21-17806954-C-G

Variant summary

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

The NM_001100420.2(C21orf91):​c.128-9836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,050 control chromosomes in the GnomAD database, including 3,443 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 0.21 (3443 hom., cov: 32)
• Consequence: C21orf91 NM_001100420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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 = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C21orf91	NM_001100420.2	c.128-9836G>A		intron_variant		ENST00000284881.9
LOC124900465	XR_007067823.1	n.1605+50165C>T		intron_variant, non_coding_transcript_variant
C21orf91	NM_001100421.2	c.128-9836G>A		intron_variant
C21orf91	NM_017447.4	c.128-9836G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C21orf91	ENST00000284881.9	c.128-9836G>A		intron_variant		2	NM_001100420.2	P4
	ENST00000428689.5	n.72-3541C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31441 AN: 151934 Hom.: 3439 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.207 AC: 31453 AN: 152050 Hom.: 3443 Cov.: 32 AF XY: 0.205 AC XY: 15233 AN XY: 74340

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.170

Alfa AF: 0.199 Hom.: 6222

Bravo AF: 0.218

Asia WGS AF: 0.268 AC: 933 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	0.92
DANN	Benign	0.63

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: rs2824499; hg19: chr21-19179271;