chr3-26710245-C-T

Variant names:

• chr3-26710245-C-T
• rs146526715
• NM_052953.4:c.573C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_052953.4(LRRC3B):​c.573C>T​(p.Asp191Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,613,712 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (54 hom.)
• Consequence: LRRC3B NM_052953.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.496
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 3-26710245-C-T is Benign according to our data. Variant chr3-26710245-C-T is described in ClinVar as Benign. ClinVar VariationId is 774296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.496 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 gene

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.573C>T	p.Asp191Asp	synonymous	Exon 2 of 2	NP_443185.1	Q96PB8
	LRRC3B	NM_001317808.2		c.573C>T	p.Asp191Asp	synonymous	Exon 2 of 2	NP_001304737.1	Q96PB8
	LRRC3B	NM_001317809.2		c.573C>T	p.Asp191Asp	synonymous	Exon 2 of 2	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.573C>T	p.Asp191Asp	synonymous	Exon 2 of 2	ENSP00000379880.2	Q96PB8
	LRRC3B	ENST00000417744.5	TSL:1	c.573C>T	p.Asp191Asp	synonymous	Exon 3 of 3	ENSP00000406370.1	Q96PB8
	LRRC3B	ENST00000456208.2	TSL:1	c.573C>T	p.Asp191Asp	synonymous	Exon 3 of 3	ENSP00000394940.2	Q96PB8

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 943 AN: 152152 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00624 AC: 1558 AN: 249524 AF XY: 0.00614

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.00412

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.00764

Gnomad OTH exome AF: 0.00741

GnomAD4 exome AF: 0.00717 AC: 10478 AN: 1461442 Hom.: 54 Cov.: 32 AF XY: 0.00705 AC XY: 5129 AN XY: 727018

African (AFR) AF: 0.00170 AC: 57 AN: 33472

American (AMR) AF: 0.00470 AC: 210 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 290 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39612

South Asian (SAS) AF: 0.00111 AC: 96 AN: 86206

European-Finnish (FIN) AF: 0.0175 AC: 934 AN: 53358

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.00756 AC: 8409 AN: 1111840

Other (OTH) AF: 0.00747 AC: 451 AN: 60376

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152270 Hom.: 7 Cov.: 33 AF XY: 0.00643 AC XY: 479 AN XY: 74452

African (AFR) AF: 0.00130 AC: 54 AN: 41538

American (AMR) AF: 0.00595 AC: 91 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.0167 AC: 177 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00779 AC: 530 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00730 Hom.: 4

Bravo AF: 0.00517

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00767

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.4
DANN	Benign	0.85
PhyloP100		-0.50
Mutation Taster		=97/3	polymorphism

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: rs146526715; hg19: chr3-26751736; COSMIC: COSV67520041; COSMIC: COSV67520041;