rs12529198

Positions:

• chr6-5151013-A-G

Variant summary

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

The NM_020408.6(LYRM4):​c.208-41522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,030 control chromosomes in the GnomAD database, including 963 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 0.10 (963 hom., cov: 32)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM4	NM_020408.6	c.208-41522T>C		intron_variant		ENST00000330636.9	NP_065141.3
LYRM4-AS1	NR_126015.1	n.373+78279A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM4	ENST00000330636.9	c.208-41522T>C		intron_variant		1	NM_020408.6	ENSP00000418787	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15375 AN: 151918 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.101 AC: 15381 AN: 152030 Hom.: 963 Cov.: 32 AF XY: 0.104 AC XY: 7732 AN XY: 74312

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0844 Hom.: 480

Bravo AF: 0.106

Asia WGS AF: 0.208 AC: 723 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	0.90
DANN	Benign	0.46

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: rs12529198; hg19: chr6-5151247;