Genetic Variant ENST00000512516.1:n.256+108C>T (chr4-177245920-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000512516.1(ENSG00000287544):n.256+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 186,906 control chromosomes in the GnomAD database, including 22,814 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 0.49 ( 18628 hom., cov: 34)

Exomes 𝑓: 0.49 ( 4186 hom. )

Consequence

ENSG00000287544
ENST00000512516.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

Publications

7 publications found

Variant links:

Genes affected

ENSG00000287544 (HGNC:):

ENSG00000287544 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105377557	XR_001741925.2 link	n.235-25245C>T	intron_variant	Intron 1 of 2
LOC105377557	XR_007058380.1 link	n.235-25245C>T	intron_variant	Intron 1 of 1
LOC105377557	XR_007058381.1 link	n.1902+24943C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000287544	ENST00000512516.1 link	n.256+108C>T	intron_variant	Intron 3 of 3	3
ENSG00000287544	ENST00000656694.1 link	n.113-25245C>T	intron_variant	Intron 1 of 4
ENSG00000287544	ENST00000662794.1 link	n.185+24943C>T	intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74926

AN:

151894

Hom.:

18614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.528

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.530

GnomAD4 exome

AF:

0.488

AC:

17035

AN:

34894

Hom.:

4186

AF XY:

0.480

AC XY:

9630

AN XY:

20050

show subpopulations

African (AFR)

AF:

0.516

AC:

332

AN:

644

American (AMR)

AF:

0.401

AC:

711

AN:

1774

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

566

AN:

890

East Asian (EAS)

AF:

0.491

AC:

320

AN:

652

South Asian (SAS)

AF:

0.447

AC:

3755

AN:

8400

European-Finnish (FIN)

AF:

0.489

AC:

1510

AN:

3086

Middle Eastern (MID)

AF:

0.583

AC:

443

AN:

760

European-Non Finnish (NFE)

AF:

0.503

AC:

8537

AN:

16974

Other (OTH)

AF:

0.502

AC:

861

AN:

1714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

443

885

1328

1770

2213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.493

AC:

74990

AN:

152012

Hom.:

18628

Cov.:

AF XY:

0.492

AC XY:

36580

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.483

AC:

20025

AN:

41476

American (AMR)

AF:

0.459

AC:

7009

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2299

AN:

3472

East Asian (EAS)

AF:

0.482

AC:

2493

AN:

5172

South Asian (SAS)

AF:

0.437

AC:

2102

AN:

4814

European-Finnish (FIN)

AF:

0.481

AC:

5064

AN:

10536

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34217

AN:

67968

Other (OTH)

AF:

0.535

AC:

1129

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1983

3965

5948

7930

9913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.506

Hom.:

66842

Bravo

AF:

0.488

Asia WGS

AF:

0.470

AC:

1636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.72

PhyloP100

0.56

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