NR_126015.1:n.238-17033A>G

Variant names:

• chr6-5055566-A-G
• rs1122637
• NR_126015.1:n.238-17033A>G

Variant summary

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

The NR_126015.1(LYRM4-AS1):​n.238-17033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,026 control chromosomes in the GnomAD database, including 6,117 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 0.22 (6117 hom., cov: 32)
• Consequence: LYRM4-AS1 NR_126015.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• Publications: 2 publications found

Genes affected

LYRM4-AS1 (HGNC:52055): (LYRM4 antisense RNA 1)

LYRM4 (HGNC:21365): (LYR motif containing 4) The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016]

LYRM4 Gene-Disease associations (from GenCC):

• severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• combined oxidative phosphorylation deficiency 19

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM4-AS1	NR_126015.1	n.238-17033A>G		intron_variant	Intron 2 of 3
LYRM4	XM_017011084.3	c.208-1408T>C		intron_variant	Intron 2 of 3		XP_016866573.1
LYRM4	XM_017011083.3	c.208-1408T>C		intron_variant	Intron 2 of 3		XP_016866572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33345 AN: 151908 Hom.: 6088 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.220 AC: 33431 AN: 152026 Hom.: 6117 Cov.: 32 AF XY: 0.219 AC XY: 16269 AN XY: 74300

African (AFR) AF: 0.505 AC: 20927 AN: 41416

American (AMR) AF: 0.135 AC: 2069 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3472

East Asian (EAS) AF: 0.132 AC: 681 AN: 5176

South Asian (SAS) AF: 0.185 AC: 889 AN: 4806

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6703 AN: 67976

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.0828 Hom.: 179

Bravo AF: 0.234

Asia WGS AF: 0.171 AC: 596 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	1.5
DANN	Benign	0.21
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs1122637; hg19: chr6-5055800;