rs8111930

Variant names:

• chr19-10257374-A-G
• rs8111930
• NM_015956.3:c.445+549A>G

Variant summary

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

The NM_015956.3(MRPL4):​c.445+549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,130 control chromosomes in the GnomAD database, including 63,171 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 0.91 (63171 hom., cov: 30)
• Consequence: MRPL4 NM_015956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 19 publications found

Genes affected

MRPL4 (HGNC:14276): (mitochondrial ribosomal protein L4) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Sequence analysis identified alternatively spliced variants that encode different protein isoforms. [provided by RefSeq, Jul 2008]

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL4	NM_015956.3	c.445+549A>G		intron_variant	Intron 5 of 8	ENST00000253099.11	NP_057040.2
MRPL4	NM_001411149.1	c.445+549A>G		intron_variant	Intron 5 of 8		NP_001398078.1
MRPL4	NM_146387.2	c.445+549A>G		intron_variant	Intron 6 of 9		NP_666499.1
MRPL4	NM_146388.2	c.445+549A>G		intron_variant	Intron 5 of 7		NP_666500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL4	ENST00000253099.11	c.445+549A>G		intron_variant	Intron 5 of 8	1	NM_015956.3	ENSP00000253099.5

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138357 AN: 152012 Hom.: 63116 Cov.: 30

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.910 AC: 138467 AN: 152130 Hom.: 63171 Cov.: 30 AF XY: 0.912 AC XY: 67801 AN XY: 74354

African (AFR) AF: 0.971 AC: 40302 AN: 41514

American (AMR) AF: 0.896 AC: 13679 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2879 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4725 AN: 5154

South Asian (SAS) AF: 0.927 AC: 4470 AN: 4824

European-Finnish (FIN) AF: 0.919 AC: 9743 AN: 10596

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59715 AN: 67986

Other (OTH) AF: 0.888 AC: 1873 AN: 2110

Alfa AF: 0.885 Hom.: 116262

Bravo AF: 0.909

Asia WGS AF: 0.927 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.038
DANN	Benign	0.58
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8111930; hg19: chr19-10368050;