Genetic Variant ENST00000342991.10:n.1274T>G (chr6-32007374-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000342991.10(ENSG00000290788):n.1274T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,341,104 control chromosomes in the GnomAD database, including 90,030 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 0.32 ( 11437 hom., cov: 26)

Exomes 𝑓: 0.21 ( 78593 hom. )

Consequence

ENSG00000290788
ENST00000342991.10 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Publications

5 publications found

Variant links:

COSMIC-nc: COSV61589954

Genes affected

ENSG00000290788 (HGNC:):

ENSG00000290788 links:

CYP21A1P (HGNC:2599): (cytochrome P450 family 21 subfamily A member 1, pseudogene)

CYP21A1P 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=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP21A1P	NR_040090.1 link	n.1274T>G		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290788	ENST00000342991.10 link	n.1274T>G		non_coding_transcript_exon_variant	Exon 5 of 8	3
CYP21A1P	ENST00000354927.4 link	n.836T>G		non_coding_transcript_exon_variant	Exon 7 of 10	6

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

44500

AN:

137376

Hom.:

11424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.340

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.253

AC:

56949

AN:

225024

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.565

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.206

AC:

248476

AN:

1203630

Hom.:

78593

Cov.:

AF XY:

0.213

AC XY:

127899

AN XY:

601202

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.572

AC:

15129

AN:

26466

American (AMR)

AF:

0.173

AC:

6694

AN:

38752

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

4630

AN:

22282

East Asian (EAS)

AF:

0.214

AC:

7764

AN:

36362

South Asian (SAS)

AF:

0.421

AC:

31662

AN:

75164

European-Finnish (FIN)

AF:

0.134

AC:

6583

AN:

49164

Middle Eastern (MID)

AF:

0.217

AC:

1041

AN:

4790

European-Non Finnish (NFE)

AF:

0.181

AC:

162682

AN:

899838

Other (OTH)

AF:

0.242

AC:

12291

AN:

50812

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.361

Heterozygous variant carriers

4838

9676

14514

19352

24190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3486

6972

10458

13944

17430

<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:

0.324

AC:

44544

AN:

137474

Hom.:

11437

Cov.:

AF XY:

0.320

AC XY:

21427

AN XY:

67016

show subpopulations

African (AFR)

AF:

0.546

AC:

19674

AN:

36002

American (AMR)

AF:

0.284

AC:

3970

AN:

14002

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

849

AN:

3200

East Asian (EAS)

AF:

0.204

AC:

978

AN:

4784

South Asian (SAS)

AF:

0.418

AC:

1783

AN:

4262

European-Finnish (FIN)

AF:

0.134

AC:

1299

AN:

9686

Middle Eastern (MID)

AF:

0.332

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.240

AC:

15039

AN:

62586

Other (OTH)

AF:

0.355

AC:

661

AN:

1864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

856

1712

2569

3425

4281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.283

Hom.:

1748

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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