Genetic Variant ENSG00000256654:n.1285T>G (chr12-5022387-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 ENST00000540533.2(ENSG00000256654):n.1285T>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 0.394 in 152,124 control chromosomes in the GnomAD database, including 12,672 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 0.39 ( 12672 hom., cov: 33)

Exomes 𝑓: 0.44 ( 0 hom. )

Consequence

ENSG00000256654
ENST00000540533.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Publications

5 publications found

Variant links:

Genes affected

ENSG00000256654 (HGNC:):

ENSG00000256654 links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC100507560	NR_187672.1 link	n.4121-104T>G	intron_variant	Intron 2 of 5
LOC100507560	NR_187673.1 link	n.4047-104T>G	intron_variant	Intron 2 of 5
LOC100507560	NR_187674.1 link	n.4121-104T>G	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000256654	ENST00000540533.2 link	n.1285T>G	non_coding_transcript_exon_variant	Exon 2 of 4	5
ENSG00000256654	ENST00000639114.2 link	n.1001T>G	non_coding_transcript_exon_variant	Exon 1 of 3	5
ENSG00000256654	ENST00000638455.1 link	n.610-104T>G	intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59919

AN:

151990

Hom.:

12660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.388

GnomAD4 exome

AF:

0.438

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.429

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000160560), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.346

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

AF:

0.394

AC:

59961

AN:

152108

Hom.:

12672

Cov.:

AF XY:

0.400

AC XY:

29761

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.400

AC:

16570

AN:

41472

American (AMR)

AF:

0.402

AC:

6148

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1457

AN:

3470

East Asian (EAS)

AF:

0.863

AC:

4466

AN:

5172

South Asian (SAS)

AF:

0.597

AC:

2878

AN:

4820

European-Finnish (FIN)

AF:

0.350

AC:

3708

AN:

10596

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23581

AN:

67974

Other (OTH)

AF:

0.391

AC:

824

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1840

3680

5519

7359

9199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.371

Hom.:

16352

Bravo

AF:

0.397

Asia WGS

AF:

0.702

AC:

2434

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.7

(source)

DANN

Benign

0.68

PhyloP100

0.43

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