rs6512265

chr19-18392025-G-Achr19-18392025-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145256.3(LRRC25):c.880C>T(p.Pro294Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,584 control chromosomes in the GnomAD database, including 369,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.72 (39954 hom., cov: 31)
  • Exomes 𝑓: 0.67 (329360 hom.)
• Consequence: LRRC25 NM_145256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

Genes affected

LRRC25 (HGNC:29806): (leucine rich repeat containing 25) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.648493E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC25	NM_145256.3	c.880C>T	p.Pro294Ser	missense_variant	2/2	ENST00000339007.4
LRRC25	XM_005259739.5	c.880C>T	p.Pro294Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC25	ENST00000339007.4	c.880C>T	p.Pro294Ser	missense_variant	2/2	1	NM_145256.3	P1
LRRC25	ENST00000595840.1	c.880C>T	p.Pro294Ser	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109515 AN: 151908 Hom.: 39912 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.668

GnomAD3 exomes AF: 0.693 AC: 174049 AN: 251114 Hom.: 60759 AF XY: 0.686 AC XY: 93107 AN XY: 135748

Gnomad AFR exome AF: 0.831

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.653

Gnomad SAS exome AF: 0.637

Gnomad FIN exome AF: 0.795

Gnomad NFE exome AF: 0.671

Gnomad OTH exome AF: 0.665

GnomAD4 exome AF: 0.670 AC: 979326 AN: 1461558 Hom.: 329360 Cov.: 54 AF XY: 0.668 AC XY: 485428 AN XY: 727096

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.791

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.721 AC: 109614 AN: 152026 Hom.: 39954 Cov.: 31 AF XY: 0.724 AC XY: 53804 AN XY: 74300

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.664

Alfa AF: 0.671 Hom.: 88795

Bravo AF: 0.718

TwinsUK AF: 0.667 AC: 2475

ALSPAC AF: 0.665 AC: 2562

ESP6500AA AF: 0.835 AC: 3679

ESP6500EA AF: 0.659 AC: 5668

ExAC AF: 0.691 AC: 83914

Asia WGS AF: 0.659 AC: 2294 AN: 3478

EpiCase AF: 0.652

EpiControl AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.9
Dann	Benign	0.97
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
MetaRNN	Benign	8.6e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.013
Sift	Benign	0.070	T;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.027	B;B
Vest4		0.019
MPC		0.46
ClinPred		0.0098	T
GERP RS		-1.6
Varity_R		0.043
gMVP		0.41

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: rs6512265; hg19: chr19-18502835; COSMIC: COSV99416026; COSMIC: COSV99416026;