3-46603419-T-G

Position:

• chr3-46603419-T-G

Variant summary

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

The ENST00000505797.1(ENSG00000283877):​n.*194+6783T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,962 control chromosomes in the GnomAD database, including 4,429 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 0.24 (4429 hom., cov: 32)
• Consequence: ENSG00000283877 ENST00000505797.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

Genes affected

ENSG00000283877 (HGNC:):

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.46603419T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283877	ENST00000505797.1	n.*194+6783T>G		intron_variant		3		ENSP00000490854.1
LRRC2	ENST00000682605.1	c.-20+3390A>C		intron_variant				ENSP00000507018.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36369 AN: 151842 Hom.: 4422 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.239 AC: 36393 AN: 151962 Hom.: 4429 Cov.: 32 AF XY: 0.233 AC XY: 17346 AN XY: 74308

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.275

Alfa AF: 0.259 Hom.: 10594

Bravo AF: 0.252

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6799581; hg19: chr3-46644909;