rs17018468

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3B	NM_052953.4	MANE Select	c.-161+22849A>G		intron	N/A	NP_443185.1
	LRRC3B	NM_001317808.2		c.-161+22222A>G		intron	N/A	NP_001304737.1
	LRRC3B	NM_001317809.2		c.-161+21728A>G		intron	N/A	NP_001304738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3B	ENST00000396641.7	TSL:1 MANE Select	c.-161+22849A>G		intron	N/A	ENSP00000379880.2
	LRRC3B	ENST00000417744.5	TSL:1	c.-161+20575A>G		intron	N/A	ENSP00000406370.1
	LRRC3B	ENST00000891723.1		c.-161+22034A>G		intron	N/A	ENSP00000561782.1

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

African (AFR) AF: 0.144 AC: 5966 AN: 41504

American (AMR) AF: 0.105 AC: 1611 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1458 AN: 5152

South Asian (SAS) AF: 0.238 AC: 1150 AN: 4826

European-Finnish (FIN) AF: 0.0717 AC: 760 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6706 AN: 67988

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.110 Hom.: 3448

Bravo AF: 0.129

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.29
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: rs17018468; hg19: chr3-26687577;