rs1047978

Variant names:

• chr21-17796838-G-C
• rs1047978
• NM_001100420.2:c.408C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-17796838-G-C
• chr21-17796838-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100420.2(C21orf91):​c.408C>G​(p.Asp136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,613,078 control chromosomes in the GnomAD database, including 91,237 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 0.27 (6842 hom., cov: 33)
  • Exomes 𝑓: 0.34 (84395 hom.)
• Consequence: C21orf91 NM_001100420.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• Publications: 27 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 (MetaRNN=0.0028917491).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100420.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	NM_001100420.2	MANE Select	c.408C>G	p.Asp136Glu	missense	Exon 3 of 5	NP_001093890.1
	C21orf91	NM_017447.4		c.408C>G	p.Asp136Glu	missense	Exon 3 of 5	NP_059143.3
	C21orf91	NM_001100421.2		c.408C>G	p.Asp136Glu	missense	Exon 3 of 4	NP_001093891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	ENST00000284881.9	TSL:2 MANE Select	c.408C>G	p.Asp136Glu	missense	Exon 3 of 5	ENSP00000284881.4
	C21orf91	ENST00000400558.7	TSL:1	c.408C>G	p.Asp136Glu	missense	Exon 3 of 4	ENSP00000383403.3
	C21orf91	ENST00000400559.7	TSL:5	c.408C>G	p.Asp136Glu	missense	Exon 3 of 5	ENSP00000383404.3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41754 AN: 152010 Hom.: 6843 Cov.: 33

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.294

GnomAD2 exomes AF: 0.325 AC: 80867 AN: 249164 AF XY: 0.328

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.343

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.336 AC: 491408 AN: 1460950 Hom.: 84395 Cov.: 35 AF XY: 0.336 AC XY: 244356 AN XY: 726816

African (AFR) AF: 0.0716 AC: 2398 AN: 33478

American (AMR) AF: 0.327 AC: 14637 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7861 AN: 26116

East Asian (EAS) AF: 0.364 AC: 14452 AN: 39684

South Asian (SAS) AF: 0.306 AC: 26424 AN: 86236

European-Finnish (FIN) AF: 0.398 AC: 21206 AN: 53308

Middle Eastern (MID) AF: 0.323 AC: 1865 AN: 5768

European-Non Finnish (NFE) AF: 0.345 AC: 383035 AN: 1111266

Other (OTH) AF: 0.323 AC: 19530 AN: 60372

GnomAD4 genome AF: 0.274 AC: 41757 AN: 152128 Hom.: 6842 Cov.: 33 AF XY: 0.278 AC XY: 20672 AN XY: 74340

African (AFR) AF: 0.0852 AC: 3539 AN: 41558

American (AMR) AF: 0.317 AC: 4844 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1008 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1784 AN: 5172

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4399 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23594 AN: 67954

Other (OTH) AF: 0.289 AC: 610 AN: 2110

Alfa AF: 0.330 Hom.: 6514

Bravo AF: 0.260

TwinsUK AF: 0.341 AC: 1264

ALSPAC AF: 0.335 AC: 1293

ESP6500AA AF: 0.0707 AC: 258

ESP6500EA AF: 0.344 AC: 2813

ExAC AF: 0.319 AC: 38518

Asia WGS AF: 0.286 AC: 994 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.92
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.15
Sift	Benign	0.053	T
Sift4G	Uncertain	0.020	D
Vest4		0.25
MutPred		0.34		Gain of disorder (P = 0.1272)
MPC		0.55
ClinPred		0.027	T
GERP RS		3.4
gMVP		0.35
Mutation Taster		=99/1	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: rs1047978; hg19: chr21-19169155; COSMIC: COSV53032600; COSMIC: COSV53032600;