6-5186666-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020408.6(LYRM4):c.207+29952C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 981,958 control chromosomes in the GnomAD database, including 32,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6820 hom., cov: 32)
  • Exomes 𝑓: 0.25 (25981 hom.)
• Consequence: LYRM4 NM_020408.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-5186666-G-T is Benign according to our data. Variant chr6-5186666-G-T is described in ClinVar as [Benign]. Clinvar id is 1283276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYRM4	NM_020408.6	c.207+29952C>A		intron_variant		ENST00000330636.9
LYRM4-AS1	NR_126015.1	n.374-51042G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYRM4	ENST00000330636.9	c.207+29952C>A		intron_variant		1	NM_020408.6	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44470 AN: 151952 Hom.: 6815 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.247 AC: 205334 AN: 829888 Hom.: 25981 Cov.: 26 AF XY: 0.247 AC XY: 94688 AN XY: 383506

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.293 AC: 44495 AN: 152070 Hom.: 6820 Cov.: 32 AF XY: 0.290 AC XY: 21575 AN XY: 74324

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.294

Alfa AF: 0.145 Hom.: 274

Bravo AF: 0.302

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.21
Dann	Benign	0.26

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: rs1055415; hg19: chr6-5186900; COSMIC: COSV105888633;