Genetic Variant ERAL1:c.284-127C>T (chr17-28856137-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 NM_005702.4(ERAL1):c.284-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000927 in 1,079,204 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 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ERAL1
NM_005702.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.304

Variant links:

Genes affected

ERAL1 (HGNC:3424): (Era like 12S mitochondrial rRNA chaperone 1) The protein encoded by this gene is a GTPase that localizes to the mitochondrion. The encoded protein binds to the 3' terminal stem loop of 12S mitochondrial rRNA and is required for proper assembly of the 28S small mitochondrial ribosomal subunit. Deletion of this gene has been shown to cause mitochondrial dysfunction, growth retardation, and apoptosis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ERAL1 links:

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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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ERAL1	NM_005702.4 link	c.284-127C>T	intron_variant	Intron 1 of 9	ENST00000254928.10	NP_005693.1	O75616-1
ERAL1	NM_001317985.2 link	c.284-127C>T	intron_variant	Intron 1 of 9		NP_001304914.1	O75616
ERAL1	NM_001317986.2 link	c.284-127C>T	intron_variant	Intron 1 of 8		NP_001304915.1	O75616
ERAL1	NR_134328.2 link	n.303-127C>T	intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAL1	ENST00000254928.10 link	c.284-127C>T		intron_variant	Intron 1 of 9	1	NM_005702.4	ENSP00000254928.5		O75616-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000431

AC:

AN:

927196

Hom.:

AF XY:

0.00000212

AC XY:

AN XY:

470896

show subpopulations

African (AFR)

AF:

0.000178

AC:

AN:

22488

American (AMR)

AF:

0.00

AC:

AN:

30546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17820

East Asian (EAS)

AF:

0.00

AC:

AN:

36842

South Asian (SAS)

AF:

0.00

AC:

AN:

62264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3804

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

669918

Other (OTH)

AF:

0.00

AC:

AN:

42228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.9

(source)

DANN

Benign

0.86

PhyloP100

-0.30

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

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chr17-28856137-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over