dbSNP rs8138979: ENSG00000224277:n.308-1G>A (chr22-23568559-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 ENST00000454863.4(ENSG00000224277):n.308-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,242 control chromosomes in the GnomAD database, including 19,108 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 0.42 ( 19107 hom., cov: 30)

Exomes 𝑓: 0.31 ( 1 hom. )

Consequence

ENSG00000224277
ENST00000454863.4 splice_acceptor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.973

Publications

6 publications found

Variant links:

Genes affected

ENSG00000224277 (HGNC:):

ENSG00000224277 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=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105372957	XR_938075.2 link	n.1129-1G>A	splice_acceptor_variant, intron_variant	Intron 1 of 2
LOC105372957	XR_938076.1 link	n.610-1G>A	splice_acceptor_variant, intron_variant	Intron 2 of 3
LOC105372957	XR_938077.2 link	n.1129-1G>A	splice_acceptor_variant, intron_variant	Intron 1 of 2
LOC105372957	XR_938078.2 link	n.1129-1G>A	splice_acceptor_variant, intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000224277	ENST00000454863.4 link	n.308-1G>A		splice_acceptor_variant, intron_variant	Intron 2 of 4	4
ENSG00000224277	ENST00000458318.2 link	n.308-1G>A		splice_acceptor_variant, intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63318

AN:

151108

Hom.:

19049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.308

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.222

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.420

AC:

63442

AN:

151216

Hom.:

19107

Cov.:

AF XY:

0.419

AC XY:

30917

AN XY:

73794

show subpopulations

African (AFR)

AF:

0.846

AC:

34794

AN:

41106

American (AMR)

AF:

0.405

AC:

6156

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3468

East Asian (EAS)

AF:

0.448

AC:

2290

AN:

5106

South Asian (SAS)

AF:

0.349

AC:

1674

AN:

4792

European-Finnish (FIN)

AF:

0.238

AC:

2455

AN:

10332

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14022

AN:

67898

Other (OTH)

AF:

0.390

AC:

821

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1244

2488

3731

4975

6219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.421

Hom.:

14229

Bravo

AF:

0.453

Asia WGS

AF:

0.483

AC:

1675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.9

(source)

DANN

Benign

0.56

PhyloP100

-0.97

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