chr21-17789372-C-T

Position:

• chr21-17789372-C-T

Variant summary

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

The NM_001100420.2(C21orf91):​c.*4043G>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 0.471 in 151,718 control chromosomes in the GnomAD database, including 16,968 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 0.47 (16968 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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)

LOC124900465 (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 (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.*4043G>A		3_prime_UTR_variant	5/5	ENST00000284881.9	NP_001093890.1
C21orf91-OT1	NR_038870.1	n.34-2162G>A		intron_variant, non_coding_transcript_variant
LOC124900465	XR_007067823.1	n.1605+32583C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.*4043G>A		3_prime_UTR_variant	5/5	2	NM_001100420.2	ENSP00000284881	P4
C21orf91-OT1	ENST00000430401.5	n.34-2162G>A		intron_variant, non_coding_transcript_variant		1
C21orf91-OT1	ENST00000430815.5	n.48-2162G>A		intron_variant, non_coding_transcript_variant		5
C21orf91-OT1	ENST00000439392.1	n.34-2162G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71427 AN: 151600 Hom.: 16951 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.471 AC: 71493 AN: 151718 Hom.: 16968 Cov.: 31 AF XY: 0.474 AC XY: 35138 AN XY: 74132

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.501

Alfa AF: 0.471 Hom.: 28191

Bravo AF: 0.467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
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: rs243609; hg19: chr21-19161689;