Genetic Variant NM_024627.6:c.-225-187G>C (chr22-19852673-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024627.6(RTL10):c.-225-187G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,126 control chromosomes in the GnomAD database, including 2,351 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 0.16 ( 2351 hom., cov: 33)

Consequence

RTL10
NM_024627.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.521

Publications

12 publications found

Variant links:

Genes affected

RTL10 (HGNC:26112): (retrotransposon Gag like 10) Involved in mitochondrial outer membrane permeabilization and regulation of mitochondrial membrane potential. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

RTL10 links:

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

GNB1L 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTL10	NM_024627.6 link	c.-225-187G>C		intron_variant	Intron 2 of 2	ENST00000328554.9	NP_078903.3	Q7L3V2
GNB1L	NM_053004.3 link	c.-21+1770G>C		intron_variant	Intron 2 of 7	ENST00000329517.11	NP_443730.1	Q9BYB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL10	ENST00000328554.9 link	c.-225-187G>C		intron_variant	Intron 2 of 2	1	NM_024627.6	ENSP00000330596.4		Q7L3V2
GNB1L	ENST00000329517.11 link	c.-21+1770G>C		intron_variant	Intron 2 of 7	1	NM_053004.3	ENSP00000331313.6		Q9BYB4-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23881

AN:

152008

Hom.:

2347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.157

AC:

23895

AN:

152126

Hom.:

2351

Cov.:

AF XY:

0.157

AC XY:

11652

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0384

AC:

1596

AN:

41520

American (AMR)

AF:

0.191

AC:

2917

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1052

AN:

3470

East Asian (EAS)

AF:

0.201

AC:

1041

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

666

AN:

4820

European-Finnish (FIN)

AF:

0.169

AC:

1794

AN:

10590

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14150

AN:

67964

Other (OTH)

AF:

0.189

AC:

398

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

982

1964

2945

3927

4909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.182

Hom.:

347

Bravo

AF:

0.155

Asia WGS

AF:

0.161

AC:

561

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.67

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over