10-132348013-C-T

Position:

• chr10-132348013-C-T

Variant summary

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

The NM_030626.3(LRRC27):​c.583C>T​(p.Arg195Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,611,388 control chromosomes in the GnomAD database, including 34,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.15 (2187 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32565 hom.)
• Consequence: LRRC27 NM_030626.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

Genes affected

LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

LRRC27 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005176842).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC27	NM_030626.3	c.583C>T	p.Arg195Cys	missense_variant	6/11	ENST00000368614.8	NP_085129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC27	ENST00000368614.8	c.583C>T	p.Arg195Cys	missense_variant	6/11	1	NM_030626.3	ENSP00000357603.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23175 AN: 152086 Hom.: 2190 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.149 AC: 37375 AN: 250450 Hom.: 3719 AF XY: 0.152 AC XY: 20528 AN XY: 135450

Gnomad AFR exome AF: 0.0666

Gnomad AMR exome AF: 0.0980

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.000382

Gnomad SAS exome AF: 0.0681

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.201 AC: 292912 AN: 1459184 Hom.: 32565 Cov.: 33 AF XY: 0.197 AC XY: 143072 AN XY: 725818

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0691

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.152 AC: 23168 AN: 152204 Hom.: 2187 Cov.: 32 AF XY: 0.144 AC XY: 10688 AN XY: 74416

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.153

Alfa AF: 0.201 Hom.: 8640

Bravo AF: 0.153

TwinsUK AF: 0.231 AC: 856

ALSPAC AF: 0.232 AC: 895

ESP6500AA AF: 0.0685 AC: 302

ESP6500EA AF: 0.226 AC: 1941

ExAC AF: 0.151 AC: 18331

Asia WGS AF: 0.0320 AC: 114 AN: 3478

EpiCase AF: 0.228

EpiControl AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.1
DANN	Benign	0.90
DEOGEN2	Benign	0.029	.;.;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.64	T;T;.;T;T
MetaRNN	Benign	0.0052	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N;N;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.2	N;.;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.10	T;.;T;T;T
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		0.0040	B;B;B;B;B
Vest4		0.051
MPC		0.081
ClinPred		0.0018	T
GERP RS		-0.65
Varity_R		0.057
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2474329; hg19: chr10-134161517; COSMIC: COSV59808854; COSMIC: COSV59808854;