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:

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new If you want to explore the variant's impact on the transcript ENST00000540533.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540533.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
LOC100507560	NR_187672.1	n.4121-104T>G	intron	N/A
LOC100507560	NR_187673.1	n.4047-104T>G	intron	N/A
LOC100507560	NR_187674.1	n.4121-104T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000256654	ENST00000540533.2	TSL:5	n.1285T>G	non_coding_transcript_exon	Exon 2 of 4
ENSG00000256654	ENST00000639114.2	TSL:5	n.1001T>G	non_coding_transcript_exon	Exon 1 of 3
ENSG00000256654	ENST00000638455.1	TSL:5	n.610-104T>G	intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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