rs2746221

Variant names:

• chr6-5183580-C-T
• rs2746221
• NM_020408.6:c.207+33038G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-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 rank	MANE	Protein	UniProt
LYRM4	NM_020408.6	c.207+33038G>A		intron_variant	Intron 2 of 2	ENST00000330636.9	NP_065141.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9	c.207+33038G>A		intron_variant	Intron 2 of 2	1	NM_020408.6	ENSP00000418787.1

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

African (AFR) AF: 0.554 AC: 22935 AN: 41428

American (AMR) AF: 0.319 AC: 4869 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5170

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2849 AN: 10538

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17005 AN: 67956

Other (OTH) AF: 0.336 AC: 709 AN: 2112

Alfa AF: 0.297 Hom.: 2501

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
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2746221; hg19: chr6-5183814;