3-46528231-G-T

Variant names:

• chr3-46528231-G-T
• rs6791703
• NM_024512.5:c.774-650C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024512.5(LRRC2):​c.774-650C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,740 control chromosomes in the GnomAD database, including 20,834 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 0.51 (20834 hom., cov: 30)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.774-650C>A		intron_variant	Intron 6 of 8	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.774-650C>A		intron_variant	Intron 6 of 8	1	NM_024512.5	ENSP00000379241.3
LRRC2	ENST00000296144.3	c.774-650C>A		intron_variant	Intron 6 of 8	1		ENSP00000296144.3
LRRC2	ENST00000682605.1	c.774-650C>A		intron_variant	Intron 6 of 8			ENSP00000507018.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77711 AN: 151622 Hom.: 20828 Cov.: 30

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.512 AC: 77743 AN: 151740 Hom.: 20834 Cov.: 30 AF XY: 0.521 AC XY: 38644 AN XY: 74120

African (AFR) AF: 0.357 AC: 14760 AN: 41350

American (AMR) AF: 0.496 AC: 7563 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3466

East Asian (EAS) AF: 0.623 AC: 3213 AN: 5158

South Asian (SAS) AF: 0.651 AC: 3130 AN: 4808

European-Finnish (FIN) AF: 0.695 AC: 7286 AN: 10488

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.560 AC: 38021 AN: 67914

Other (OTH) AF: 0.496 AC: 1045 AN: 2106

Alfa AF: 0.542 Hom.: 80496

Bravo AF: 0.492

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6791703; hg19: chr3-46569721;