Genetic Variant ENSG00000256861:n.1594+6053G>A (chr12-122226273-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000535844.1(ENSG00000256861):n.1594+6053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 686,954 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ENSG00000256861
ENST00000535844.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

Publications

0 publications found

Variant links:

Genes affected

ENSG00000256861 (HGNC:):

ENSG00000256861 links:

DIABLO (HGNC:21528): (diablo IAP-binding mitochondrial protein) This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

DIABLO Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 64
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

DIABLO links:

LOC128125816 (HGNC:0):

LOC128125816 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535844.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
DIABLO	NM_019887.6	c.-259G>A	5_prime_UTR	Exon 2 of 7	NP_063940.1
DIABLO	NM_001278342.1	c.-259G>A	5_prime_UTR	Exon 1 of 5	NP_001265271.1
DIABLO	NM_138930.3	c.-389G>A	5_prime_UTR	Exon 1 of 6	NP_620308.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENSG00000256861	ENST00000535844.1	TSL:2	n.1594+6053G>A	intron	N/A	ENSP00000454454.1
ENSG00000284934	ENST00000475784.1	TSL:4	c.*157G>A	3_prime_UTR	Exon 2 of 2	ENSP00000495792.1
ENSG00000284934	ENST00000645606.1		c.*157G>A	3_prime_UTR	Exon 2 of 7	ENSP00000493911.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

535976

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

289248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15222

American (AMR)

AF:

0.00

AC:

AN:

32300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18372

East Asian (EAS)

AF:

0.0000315

AC:

AN:

31752

South Asian (SAS)

AF:

0.00

AC:

AN:

59550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2356

European-Non Finnish (NFE)

AF:

0.0000223

AC:

AN:

314384

Other (OTH)

AF:

0.00

AC:

AN:

29722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150978

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40852

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67836

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

(source)

DANN

Benign

0.89

PhyloP100

0.064

PromoterAI

-0.023

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over