Genetic Variant ENSG00000228863:n.50+6T>A (chr1-160647341-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000840727.1(ENSG00000228863):n.50+6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 176,178 control chromosomes in the GnomAD database, including 1,132 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 0.095 ( 929 hom., cov: 31)

Exomes 𝑓: 0.099 ( 203 hom. )

Consequence

ENSG00000228863
ENST00000840727.1 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

8 publications found

Variant links:

Genes affected

ENSG00000228863 (HGNC:):

ENSG00000228863 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=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985220	XR_001738266.2 link	n.327+6T>A		splice_region_variant, intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228863	ENST00000840727.1 link	n.50+6T>A		splice_region_variant, intron_variant	Intron 1 of 1
ENSG00000228863	ENST00000840728.1 link	n.302+6T>A		splice_region_variant, intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0946

AC:

14378

AN:

151996

Hom.:

928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0939

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0707

Gnomad OTH

AF:

0.0933

GnomAD4 exome

AF:

0.0991

AC:

2384

AN:

24064

Hom.:

203

Cov.:

AF XY:

0.0982

AC XY:

1234

AN XY:

12562

show subpopulations

African (AFR)

AF:

0.0660

AC:

AN:

1242

American (AMR)

AF:

0.100

AC:

288

AN:

2878

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

AN:

446

East Asian (EAS)

AF:

0.329

AC:

693

AN:

2108

South Asian (SAS)

AF:

0.0854

AC:

253

AN:

2962

European-Finnish (FIN)

AF:

0.116

AC:

AN:

658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0705

AC:

891

AN:

12630

Other (OTH)

AF:

0.0830

AC:

AN:

1072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

187

281

374

468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0947

AC:

14399

AN:

152114

Hom.:

929

Cov.:

AF XY:

0.0985

AC XY:

7326

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0942

AC:

3909

AN:

41500

American (AMR)

AF:

0.105

AC:

1610

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3466

East Asian (EAS)

AF:

0.366

AC:

1887

AN:

5160

South Asian (SAS)

AF:

0.0965

AC:

466

AN:

4828

European-Finnish (FIN)

AF:

0.133

AC:

1405

AN:

10590

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0707

AC:

4807

AN:

67978

Other (OTH)

AF:

0.0938

AC:

198

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

633

1267

1900

2534

3167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0400

Hom.:

Bravo

AF:

0.0926

Asia WGS

AF:

0.193

AC:

670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.2

(source)

DANN

Benign

0.81

PhyloP100

0.13

PromoterAI

0.033

Neutral

(source)

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