5-131182049-C-A

Position:

• chr5-131182049-C-A

Variant summary

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

The NM_181705.4(LYRM7):​c.92-180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,150 control chromosomes in the GnomAD database, including 1,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (1164 hom., cov: 31)
• Consequence: LYRM7 NM_181705.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.190

Genes affected

LYRM7 (HGNC:28072): (LYR motif containing 7) Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

HINT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-131182049-C-A is Benign according to our data. Variant chr5-131182049-C-A is described in ClinVar as [Benign]. Clinvar id is 1230914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYRM7	NM_181705.4	c.92-180C>A		intron_variant		ENST00000379380.9	NP_859056.2
LYRM7	NM_001293735.2	c.92-180C>A		intron_variant			NP_001280664.1
LYRM7	NR_121658.2	n.168+1882C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYRM7	ENST00000379380.9	c.92-180C>A		intron_variant		1	NM_181705.4	ENSP00000368688.4
LYRM7	ENST00000507584.1	c.92-180C>A		intron_variant		2		ENSP00000423991.1
LYRM7	ENST00000510516.5	c.91+1882C>A		intron_variant		2		ENSP00000423283.1
HINT1	ENST00000506207.2	n.109-10316G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11364 AN: 152032 Hom.: 1163 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00851

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0748 AC: 11381 AN: 152150 Hom.: 1164 Cov.: 31 AF XY: 0.0731 AC XY: 5442 AN XY: 74416

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00849

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0464 Hom.: 90

Bravo AF: 0.0846

Asia WGS AF: 0.0400 AC: 137 AN: 3456

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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.34

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: rs74935479; hg19: chr5-130517742;