rs3788304

Variant names:

• chr22-19852673-C-G
• rs3788304
• NM_024627.6:c.-225-187G>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.-225-187G>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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024627.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL10	NM_024627.6	MANE Select	c.-225-187G>C		intron	N/A	NP_078903.3
	GNB1L	NM_053004.3	MANE Select	c.-21+1770G>C		intron	N/A	NP_443730.1	Q9BYB4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL10	ENST00000328554.9	TSL:1 MANE Select	c.-225-187G>C		intron	N/A	ENSP00000330596.4	Q7L3V2
	GNB1L	ENST00000329517.11	TSL:1 MANE Select	c.-21+1770G>C		intron	N/A	ENSP00000331313.6	Q9BYB4-1
	RTL10	ENST00000405640.1	TSL:1	c.-225-187G>C		intron	N/A	ENSP00000384924.1	Q7L3V2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23881 AN: 152008 Hom.: 2347 Cov.: 33

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.: 33 AF XY: 0.157 AC XY: 11652 AN XY: 74368

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: 72 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14150 AN: 67964

Other (OTH) AF: 0.189 AC: 398 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.52
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: rs3788304; hg19: chr22-19840196;