rs9392653

Variant names:

• chr6-5071258-C-T
• rs9392653
• NM_001318783.1:c.208-2592G>A

Variant summary

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

The NM_001318783.1(LYRM4):​c.208-2592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,886 control chromosomes in the GnomAD database, including 6,181 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 0.28 (6181 hom., cov: 31)
• Consequence: LYRM4 NM_001318783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 6 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYRM4	NM_001318783.1	c.208-2592G>A		intron_variant	Intron 2 of 2		NP_001305712.1
LYRM4-AS1	NR_126015.1	n.238-1341C>T		intron_variant	Intron 2 of 3
LYRM4	NR_134856.1	n.517-2592G>A		intron_variant	Intron 3 of 3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42365 AN: 151768 Hom.: 6173 Cov.: 31

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.279 AC: 42400 AN: 151886 Hom.: 6181 Cov.: 31 AF XY: 0.277 AC XY: 20578 AN XY: 74246

African (AFR) AF: 0.325 AC: 13441 AN: 41362

American (AMR) AF: 0.277 AC: 4225 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3464

East Asian (EAS) AF: 0.100 AC: 519 AN: 5182

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4818

European-Finnish (FIN) AF: 0.240 AC: 2528 AN: 10518

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18480 AN: 67962

Other (OTH) AF: 0.297 AC: 628 AN: 2112

Alfa AF: 0.278 Hom.: 19416

Bravo AF: 0.284

Asia WGS AF: 0.180 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		-2.7

Splicing

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

Other links and lift over

dbSNP: rs9392653; hg19: chr6-5071492;