Genetic Variant ENSG00000283201:c.-212+938C>T (chr19-23269280-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 ENST00000611392.5(ENSG00000283201):c.-212+938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,370 control chromosomes in the GnomAD database, including 19,067 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 0.48 ( 19065 hom., cov: 29)

Exomes 𝑓: 0.27 ( 2 hom. )

Consequence

ENSG00000283201
ENST00000611392.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.889

Publications

2 publications found

Variant links:

Genes affected

ENSG00000283201 (HGNC:):

ENSG00000283201 links:

IPO5P1 (HGNC:49687): (importin 5 pseudogene 1)

IPO5P1 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5P1	NR_103741.1 link	n.251+938C>T		intron_variant	Intron 2 of 4
IPO5P1	NR_103742.1 link	n.176+4796C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283201	ENST00000611392.5 link	c.-212+938C>T		intron_variant	Intron 2 of 6	5		ENSP00000478939.2		A0A087WUU8

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72593

AN:

151224

Hom.:

19049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.491

GnomAD4 exome

AF:

0.269

AC:

AN:

Hom.:

Cov.:

AF XY:

0.208

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)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000907115), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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:

0.480

AC:

72620

AN:

151344

Hom.:

19065

Cov.:

AF XY:

0.488

AC XY:

36046

AN XY:

73920

show subpopulations

African (AFR)

AF:

0.252

AC:

10410

AN:

41320

American (AMR)

AF:

0.615

AC:

9339

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

1889

AN:

3452

East Asian (EAS)

AF:

0.688

AC:

3516

AN:

5114

South Asian (SAS)

AF:

0.573

AC:

2744

AN:

4788

European-Finnish (FIN)

AF:

0.608

AC:

6346

AN:

10442

Middle Eastern (MID)

AF:

0.497

AC:

145

AN:

292

European-Non Finnish (NFE)

AF:

0.542

AC:

36721

AN:

67746

Other (OTH)

AF:

0.489

AC:

1027

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1704

3409

5113

6818

8522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.493

Hom.:

2414

Bravo

AF:

0.473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.3

(source)

DANN

Benign

0.32

PhyloP100

-0.89

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