NM_052953.4:c.-161+20504G>A

Variant names:

• chr3-26643741-G-A
• rs7652737
• NM_052953.4:c.-161+20504G>A

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+20504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,100 control chromosomes in the GnomAD database, including 4,493 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 0.22 (4493 hom., cov: 32)
• Consequence: LRRC3B NM_052953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 3 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3B	NM_052953.4	c.-161+20504G>A		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+20504G>A		intron_variant	Intron 1 of 1	1	NM_052953.4	ENSP00000379880.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33255 AN: 151982 Hom.: 4484 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.219 AC: 33302 AN: 152100 Hom.: 4493 Cov.: 32 AF XY: 0.222 AC XY: 16530 AN XY: 74358

African (AFR) AF: 0.342 AC: 14175 AN: 41478

American (AMR) AF: 0.195 AC: 2983 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2398 AN: 5162

South Asian (SAS) AF: 0.283 AC: 1365 AN: 4816

European-Finnish (FIN) AF: 0.147 AC: 1557 AN: 10592

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9272 AN: 67970

Other (OTH) AF: 0.226 AC: 479 AN: 2116

Alfa AF: 0.159 Hom.: 3312

Bravo AF: 0.231

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.50
PhyloP100		1.9
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: rs7652737; hg19: chr3-26685232;