Genetic Variant NM_001100420.2:c.727+46A>G (chr21-17795162-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001100420.2(C21orf91):c.727+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,207,152 control chromosomes in the GnomAD database, including 31,384 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 0.24 ( 4688 hom., cov: 32)

Exomes 𝑓: 0.22 ( 26696 hom. )

Consequence

C21orf91
NM_001100420.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

20 publications found

Variant links:

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 links:

ENSG00000244676 (HGNC:):

ENSG00000244676 links:

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ACMG classification

Classification was made for transcript

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 = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C21orf91	NM_001100420.2 link	c.727+46A>G	intron_variant	Intron 4 of 4	ENST00000284881.9	NP_001093890.1	Q9NYK6-1Q68DA1
C21orf91	NM_017447.4 link	c.727+46A>G	intron_variant	Intron 4 of 4		NP_059143.3	Q9NYK6-3Q68DA1
C21orf91	NM_001100421.2 link	c.664+1420A>G	intron_variant	Intron 3 of 3		NP_001093891.1	Q9NYK6-2Q68DA1
LOC124900465	XR_007067823.1 link	n.1605+38373T>C	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9 link	c.727+46A>G		intron_variant	Intron 4 of 4	2	NM_001100420.2	ENSP00000284881.4		Q9NYK6-1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36251

AN:

152008

Hom.:

4685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.225

AC:

55821

AN:

247768

AF XY:

0.218

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.218

AC:

229990

AN:

1055026

Hom.:

26696

Cov.:

AF XY:

0.214

AC XY:

116676

AN XY:

544078

show subpopulations

African (AFR)

AF:

0.316

AC:

8172

AN:

25846

American (AMR)

AF:

0.267

AC:

11786

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

3646

AN:

23574

East Asian (EAS)

AF:

0.386

AC:

14605

AN:

37868

South Asian (SAS)

AF:

0.189

AC:

14711

AN:

77914

European-Finnish (FIN)

AF:

0.137

AC:

7171

AN:

52182

Middle Eastern (MID)

AF:

0.132

AC:

651

AN:

4926

European-Non Finnish (NFE)

AF:

0.214

AC:

158921

AN:

741568

Other (OTH)

AF:

0.220

AC:

10327

AN:

46982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9278

18556

27834

37112

46390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4756

9512

14268

19024

23780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.238

AC:

36262

AN:

152126

Hom.:

4688

Cov.:

AF XY:

0.234

AC XY:

17430

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.311

AC:

12916

AN:

41478

American (AMR)

AF:

0.261

AC:

3979

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

536

AN:

3470

East Asian (EAS)

AF:

0.397

AC:

2049

AN:

5166

South Asian (SAS)

AF:

0.193

AC:

931

AN:

4822

European-Finnish (FIN)

AF:

0.126

AC:

1337

AN:

10610

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13887

AN:

67994

Other (OTH)

AF:

0.195

AC:

412

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1365

2730

4096

5461

6826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

5180

Bravo

AF:

0.254

Asia WGS

AF:

0.281

AC:

977

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

4.6

(source)

DANN

Benign

0.68

PhyloP100

-0.32

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over