Genetic Variant ENSG00000290788:n.1140A>T (chr6-32007071-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000342991.10(ENSG00000290788):n.1140A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.000028 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000011 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000290788
ENST00000342991.10 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

35 publications found

Variant links:

COSMIC-nc: COSV99048786

Genes affected

ENSG00000290788 (HGNC:):

ENSG00000290788 links:

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

CYP21A1P links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342991.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP21A1P	NR_040090.1		n.1140A>T		non_coding_transcript_exon	Exon 4 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290788	ENST00000342991.10	TSL:3	n.1140A>T		non_coding_transcript_exon	Exon 4 of 8
	CYP21A1P	ENST00000354927.4	TSL:6	n.702A>T		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes

AF:

0.0000277

AC:

AN:

144638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000180

AC:

AN:

222212

AF XY:

0.0000167

show subpopulations

Gnomad AFR exome

AF:

0.0000724

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000306

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000107

AC:

AN:

1401096

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

695440

show subpopulations

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

African (AFR)

AF:

0.000125

AC:

AN:

31984

American (AMR)

AF:

0.00

AC:

AN:

43048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25718

East Asian (EAS)

AF:

0.00

AC:

AN:

38632

South Asian (SAS)

AF:

0.0000372

AC:

AN:

80630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50892

Middle Eastern (MID)

AF:

0.000357

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00000469

AC:

AN:

1066312

Other (OTH)

AF:

0.0000172

AC:

AN:

58274

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000276

AC:

AN:

144748

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

70716

show subpopulations

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

African (AFR)

AF:

0.0000254

AC:

AN:

39366

American (AMR)

AF:

0.00

AC:

AN:

14814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3196

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.00

AC:

AN:

4486

European-Finnish (FIN)

AF:

0.000100

AC:

AN:

9998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000309

AC:

AN:

64730

Other (OTH)

AF:

0.00

AC:

AN:

2002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000169

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over