NM_001100420.2:c.128-9836G>A

Variant names:

• chr21-17806954-C-T
• rs2824499
• NM_001100420.2:c.128-9836G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

ENSG00000244676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.128-9836G>A		intron_variant	Intron 2 of 4	ENST00000284881.9	NP_001093890.1
C21orf91	NM_017447.4	c.128-9836G>A		intron_variant	Intron 2 of 4		NP_059143.3
C21orf91	NM_001100421.2	c.128-9836G>A		intron_variant	Intron 2 of 3		NP_001093891.1
LOC124900465	XR_007067823.1	n.1605+50165C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.128-9836G>A		intron_variant	Intron 2 of 4	2	NM_001100420.2	ENSP00000284881.4

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

African (AFR) AF: 0.205 AC: 8482 AN: 41464

American (AMR) AF: 0.243 AC: 3708 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2021 AN: 5174

South Asian (SAS) AF: 0.192 AC: 925 AN: 4812

European-Finnish (FIN) AF: 0.127 AC: 1344 AN: 10578

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13863 AN: 67976

Other (OTH) AF: 0.170 AC: 359 AN: 2108

Alfa AF: 0.202 Hom.: 9973

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
PhyloP100		-0.053
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: rs2824499; hg19: chr21-19179271;