rs11704083

Variant names:

• chr22-19852890-A-G
• rs11704083
• NM_024627.6:c.-225-404T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024627.6(RTL10):​c.-225-404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,982 control chromosomes in the GnomAD database, including 24,222 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 0.54 (24222 hom., cov: 32)
• Consequence: RTL10 NM_024627.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 15 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTL10	NM_024627.6	c.-225-404T>C		intron_variant	Intron 2 of 2	ENST00000328554.9	NP_078903.3
GNB1L	NM_053004.3	c.-21+1553T>C		intron_variant	Intron 2 of 7	ENST00000329517.11	NP_443730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL10	ENST00000328554.9	c.-225-404T>C		intron_variant	Intron 2 of 2	1	NM_024627.6	ENSP00000330596.4
GNB1L	ENST00000329517.11	c.-21+1553T>C		intron_variant	Intron 2 of 7	1	NM_053004.3	ENSP00000331313.6

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82568 AN: 151864 Hom.: 24164 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.544 AC: 82695 AN: 151982 Hom.: 24222 Cov.: 32 AF XY: 0.537 AC XY: 39871 AN XY: 74302

African (AFR) AF: 0.777 AC: 32181 AN: 41442

American (AMR) AF: 0.448 AC: 6852 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2008 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1997 AN: 5172

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4818

European-Finnish (FIN) AF: 0.388 AC: 4095 AN: 10556

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32034 AN: 67922

Other (OTH) AF: 0.528 AC: 1115 AN: 2112

Alfa AF: 0.497 Hom.: 33273

Bravo AF: 0.560

Asia WGS AF: 0.402 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.25
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11704083; hg19: chr22-19840413;