rs22662

chr6-5183302-T-C

Variant summary

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

The NM_020408.6(LYRM4):c.207+33316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,032 control chromosomes in the GnomAD database, including 5,335 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 0.15 (5335 hom., cov: 33)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.207+33316A>G		intron_variant		ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.374-54406T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.207+33316A>G		intron_variant		1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22849 AN: 151912 Hom.: 5302 Cov.: 33

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0350

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.151 AC: 22929 AN: 152032 Hom.: 5335 Cov.: 33 AF XY: 0.148 AC XY: 11011 AN XY: 74358

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0349

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00406

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0186 Hom.: 642

Bravo AF: 0.170

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	5.2
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: rs22662; hg19: chr6-5183536;