19-18392025-G-A

Variant names:

• chr19-18392025-G-A
• rs6512265
• NM_145256.3:c.880C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC25	NM_145256.3	MANE Select	c.880C>T	p.Pro294Ser	missense	Exon 2 of 2	NP_660299.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC25	ENST00000339007.4	TSL:1 MANE Select	c.880C>T	p.Pro294Ser	missense	Exon 2 of 2	ENSP00000340983.2
	LRRC25	ENST00000595840.1	TSL:1	c.880C>T	p.Pro294Ser	missense	Exon 3 of 3	ENSP00000472290.1

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

GnomAD2 exomes AF: 0.693 AC: 174049 AN: 251114 AF XY: 0.686

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 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

African (AFR) AF: 0.825 AC: 27617 AN: 33478

American (AMR) AF: 0.716 AC: 32017 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17941 AN: 26132

East Asian (EAS) AF: 0.609 AC: 24163 AN: 39684

South Asian (SAS) AF: 0.636 AC: 54841 AN: 86246

European-Finnish (FIN) AF: 0.791 AC: 42235 AN: 53402

Middle Eastern (MID) AF: 0.620 AC: 3573 AN: 5766

European-Non Finnish (NFE) AF: 0.662 AC: 736294 AN: 1111758

Other (OTH) AF: 0.673 AC: 40645 AN: 60388

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

African (AFR) AF: 0.821 AC: 34073 AN: 41484

American (AMR) AF: 0.695 AC: 10599 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2435 AN: 3466

East Asian (EAS) AF: 0.652 AC: 3367 AN: 5162

South Asian (SAS) AF: 0.627 AC: 3021 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8582 AN: 10594

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45336 AN: 67938

Other (OTH) AF: 0.664 AC: 1399 AN: 2108

Alfa AF: 0.679 Hom.: 136114

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 v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	8.6e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.48
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.013
Sift	Benign	0.070	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.027	B
Vest4		0.019
MPC		0.46
ClinPred		0.0098	T
GERP RS		-1.6
Varity_R		0.043
gMVP		0.41
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: rs6512265; hg19: chr19-18502835; COSMIC: COSV99416026; COSMIC: COSV99416026;