rs2746221

Positions:

• chr6-5183580-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020408.6(LYRM4):​c.207+33038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,980 control chromosomes in the GnomAD database, including 10,202 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 0.34 (10202 hom., cov: 32)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.207+33038G>A		intron_variant		ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.374-54128C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.207+33038G>A		intron_variant		1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51873 AN: 151866 Hom.: 10174 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.342 AC: 51943 AN: 151980 Hom.: 10202 Cov.: 32 AF XY: 0.339 AC XY: 25194 AN XY: 74248

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.336

Alfa AF: 0.298 Hom.: 1249

Bravo AF: 0.358

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2746221; hg19: chr6-5183814;