rs1062202

Positions:

• chr21-17792325-A-G

Variant summary

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

The NM_001100420.2(C21orf91):​c.*1090T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,950 control chromosomes in the GnomAD database, including 9,997 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 (9997 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C21orf91	NM_001100420.2	c.*1090T>C		3_prime_UTR_variant	5/5	ENST00000284881.9
C21orf91-OT1	NR_038870.1	n.33+152T>C		intron_variant, non_coding_transcript_variant
LOC124900465	XR_007067823.1	n.1605+35536A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C21orf91	ENST00000284881.9	c.*1090T>C		3_prime_UTR_variant	5/5	2	NM_001100420.2	P4
C21orf91-OT1	ENST00000430401.5	n.33+152T>C		intron_variant, non_coding_transcript_variant		1
C21orf91-OT1	ENST00000430815.5	n.47+152T>C		intron_variant, non_coding_transcript_variant		5
C21orf91-OT1	ENST00000439392.1	n.33+152T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52168 AN: 151832 Hom.: 9983 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.292

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: 0.344 AC: 52226 AN: 151950 Hom.: 9997 Cov.: 32 AF XY: 0.339 AC XY: 25177 AN XY: 74286

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.289

Alfa AF: 0.310 Hom.: 1958

Bravo AF: 0.366

Asia WGS AF: 0.360 AC: 1251 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.45

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: rs1062202; hg19: chr21-19164642;