rs4973798

Variant names:

• chr3-26639693-G-A
• rs4973798
• NM_052953.4:c.-161+16456G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-26639693-G-A
• chr3-26639693-G-T

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+16456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,914 control chromosomes in the GnomAD database, including 26,807 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 0.59 (26807 hom., cov: 31)
• Consequence: LRRC3B NM_052953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 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+16456G>A		intron	N/A	NP_443185.1	Q96PB8
	LRRC3B	NM_001317808.2		c.-161+15829G>A		intron	N/A	NP_001304737.1	Q96PB8
	LRRC3B	NM_001317809.2		c.-161+15335G>A		intron	N/A	NP_001304738.1	Q96PB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3B	ENST00000396641.7	TSL:1 MANE Select	c.-161+16456G>A		intron	N/A	ENSP00000379880.2	Q96PB8
	LRRC3B	ENST00000417744.5	TSL:1	c.-161+14182G>A		intron	N/A	ENSP00000406370.1	Q96PB8
	LRRC3B	ENST00000891723.1		c.-161+15641G>A		intron	N/A	ENSP00000561782.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89607 AN: 151794 Hom.: 26773 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.590 AC: 89692 AN: 151914 Hom.: 26807 Cov.: 31 AF XY: 0.592 AC XY: 43906 AN XY: 74222

African (AFR) AF: 0.636 AC: 26322 AN: 41404

American (AMR) AF: 0.630 AC: 9618 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3470

East Asian (EAS) AF: 0.793 AC: 4097 AN: 5166

South Asian (SAS) AF: 0.601 AC: 2890 AN: 4810

European-Finnish (FIN) AF: 0.504 AC: 5308 AN: 10536

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37213 AN: 67938

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.557 Hom.: 3057

Bravo AF: 0.604

Asia WGS AF: 0.675 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.94
PhyloP100		-0.32
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: rs4973798; hg19: chr3-26681184;