rs4609161

Positions:

• chr8-91161887-G-A

Variant summary

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

The NM_001129890.2(LRRC69):​c.651+26148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,134 control chromosomes in the GnomAD database, including 5,441 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 0.21 (5441 hom., cov: 32)
• Consequence: LRRC69 NM_001129890.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

LRRC69 (HGNC:34303): (leucine rich repeat containing 69) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC69	NM_001129890.2	c.651+26148G>A		intron_variant		ENST00000448384.3
LRRC69	NM_001354470.2	c.184-27635G>A		intron_variant
LRRC69	NR_148895.2	n.1093+26148G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC69	ENST00000448384.3	c.651+26148G>A		intron_variant		5	NM_001129890.2	P1
LRRC69	ENST00000343709.7	c.184-27635G>A		intron_variant		2
LRRC69	ENST00000520099.5	c.*840+26148G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31752 AN: 151016 Hom.: 5424 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.210 AC: 31810 AN: 151134 Hom.: 5441 Cov.: 32 AF XY: 0.202 AC XY: 14934 AN XY: 73798

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.184

Alfa AF: 0.144 Hom.: 865

Bravo AF: 0.226

Asia WGS AF: 0.0790 AC: 276 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.20

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: rs4609161; hg19: chr8-92174115;