rs8111930

chr19-10257374-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MRPL4	NM_015956.3	c.445+549A>G		intron_variant		ENST00000253099.11
MRPL4	NM_001411149.1	c.445+549A>G		intron_variant
MRPL4	NM_146387.2	c.445+549A>G		intron_variant
MRPL4	NM_146388.2	c.445+549A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL4	ENST00000253099.11	c.445+549A>G		intron_variant		1	NM_015956.3	P1
LIMASI	ENST00000592893.1	n.358+2838T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.888

Alfa AF: 0.881 Hom.: 77683

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8111930; hg19: chr19-10368050;