Genetic Variant ENSG00000254851:n.470T>C (chr11-117138230-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000528464.1(ENSG00000254851):n.470T>C 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 0.653 in 142,668 control chromosomes in the GnomAD database, including 33,877 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 0.65 ( 33877 hom., cov: 22)

Exomes 𝑓: 0.76 ( 380610 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000254851
ENST00000528464.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Publications

10 publications found

Variant links:

Genes affected

ENSG00000254851 (HGNC:):

ENSG00000254851 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BS2

High Homozygotes in GnomAd4 at 33877 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC653303		n.117138230T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000254851	ENST00000528464.1 link	n.470T>C	non_coding_transcript_exon_variant	Exon 5 of 5	6
ENSG00000307802	ENST00000828897.1 link	n.70-529A>G	intron_variant	Intron 1 of 1
ENSG00000307802	ENST00000828898.1 link	n.54-529A>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

93088

AN:

142546

Hom.:

33875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.951

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.672

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.763

AC:

937368

AN:

1228860

Hom.:

380610

Cov.:

AF XY:

0.756

AC XY:

459805

AN XY:

607878

show subpopulations

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

African (AFR)

AF:

0.394

AC:

11409

AN:

28932

American (AMR)

AF:

0.672

AC:

20688

AN:

30786

Ashkenazi Jewish (ASJ)

AF:

0.706

AC:

13367

AN:

18930

East Asian (EAS)

AF:

0.419

AC:

15554

AN:

37158

South Asian (SAS)

AF:

0.491

AC:

32573

AN:

66384

European-Finnish (FIN)

AF:

0.754

AC:

34303

AN:

45474

Middle Eastern (MID)

AF:

0.663

AC:

2919

AN:

4404

European-Non Finnish (NFE)

AF:

0.814

AC:

769329

AN:

945230

Other (OTH)

AF:

0.722

AC:

37226

AN:

51562

⚠️ 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: 0.359

Heterozygous variant carriers

7628

15256

22884

30512

38140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17024

34048

51072

68096

85120

<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:

0.653

AC:

93116

AN:

142668

Hom.:

33877

Cov.:

AF XY:

0.643

AC XY:

44508

AN XY:

69252

show subpopulations

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

African (AFR)

AF:

0.420

AC:

16539

AN:

39392

American (AMR)

AF:

0.671

AC:

9454

AN:

14084

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2330

AN:

3234

East Asian (EAS)

AF:

0.381

AC:

1775

AN:

4656

South Asian (SAS)

AF:

0.463

AC:

1990

AN:

4298

European-Finnish (FIN)

AF:

0.735

AC:

7022

AN:

9556

Middle Eastern (MID)

AF:

0.697

AC:

184

AN:

264

European-Non Finnish (NFE)

AF:

0.803

AC:

51688

AN:

64360

Other (OTH)

AF:

0.667

AC:

1295

AN:

1942

⚠️ 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: 0.396

Heterozygous variant carriers

1115

2229

3344

4458

5573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.716

Hom.:

4699

Asia WGS

AF:

0.421

AC:

1435

AN:

3404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

2.6

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