rs9808967

chr3-46547804-A-T

Variant summary

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

The NM_024512.5(LRRC2):c.126-2551T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,096 control chromosomes in the GnomAD database, including 575 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 0.080 (575 hom., cov: 32)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC2	NM_024512.5	c.126-2551T>A		intron_variant		ENST00000395905.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC2	ENST00000395905.8	c.126-2551T>A		intron_variant		1	NM_024512.5	P1
LRRC2	ENST00000296144.3	c.126-2551T>A		intron_variant		1		P1
LRRC2	ENST00000682605.1	c.126-2551T>A		intron_variant				P1
LRRC2	ENST00000496388.1	n.349-2551T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12219 AN: 151978 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.0805 AC: 12243 AN: 152096 Hom.: 575 Cov.: 32 AF XY: 0.0851 AC XY: 6327 AN XY: 74340

Gnomad4 AFR AF: 0.0698

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0821 Hom.: 62

Bravo AF: 0.0710

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.69
Dann	Benign	0.66

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: rs9808967; hg19: chr3-46589294;