rs17018468

Variant names:

• chr3-26646086-A-G
• rs17018468
• NM_052953.4:c.-161+22849A>G

Variant summary

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

The NM_052953.4(LRRC3B):​c.-161+22849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,146 control chromosomes in the GnomAD database, including 1,415 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 0.12 (1415 hom., cov: 31)
• Consequence: LRRC3B NM_052953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

Genes affected

LRRC3B (HGNC:28105): (leucine rich repeat containing 3B) The protein encoded by this gene is a tumor suppressor, with lowered expression levels found in gastric, renal, colorectal, lung, and breast cancer tissues. The promoter of this gene is frequently hypermethylated in these cancer tissues, although the hypermethylation does not appear to be the cause of the reduced expression of this gene. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3B	NM_052953.4	c.-161+22849A>G		intron_variant	Intron 1 of 1	ENST00000396641.7	NP_443185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC3B	ENST00000396641.7	c.-161+22849A>G		intron_variant	Intron 1 of 1	1	NM_052953.4	ENSP00000379880.2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18884 AN: 152028 Hom.: 1413 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.124 AC: 18898 AN: 152146 Hom.: 1415 Cov.: 31 AF XY: 0.126 AC XY: 9384 AN XY: 74374

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.0986

Gnomad4 OTH AF: 0.139

Alfa AF: 0.109 Hom.: 1406

Bravo AF: 0.129

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.67

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: rs17018468; hg19: chr3-26687577;