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. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3B	NM_052953.4	c.-161+16456G>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+16456G>A		intron_variant	Intron 1 of 1	1	NM_052953.4	ENSP00000379880.2

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

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.626

Alfa AF: 0.555 Hom.: 2925

Bravo AF: 0.604

Asia WGS AF: 0.675 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.94

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: rs4973798; hg19: chr3-26681184;