rs35923425

Positions:

• chr3-169851644-C-G

Variant summary

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

The ENST00000316428.10(LRRC31):​c.1134G>C​(p.Leu378Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,613,726 control chromosomes in the GnomAD database, including 4,249 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.059 (339 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3910 hom.)
• Consequence: LRRC31 ENST00000316428.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026362538).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC31	NM_024727.4	c.1134G>C	p.Leu378Phe	missense_variant	7/9	ENST00000316428.10	NP_079003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC31	ENST00000316428.10	c.1134G>C	p.Leu378Phe	missense_variant	7/9	1	NM_024727.4	ENSP00000325978	P1
LRRC31	ENST00000523069.1	c.1134G>C	p.Leu378Phe	missense_variant	7/9	1		ENSP00000429145
LRRC31	ENST00000264676.9	c.966G>C	p.Leu322Phe	missense_variant	6/8	2		ENSP00000264676

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8986 AN: 152124 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0775

GnomAD3 exomes AF: 0.0714 AC: 17819 AN: 249400 Hom.: 715 AF XY: 0.0725 AC XY: 9813 AN XY: 135312

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.0971

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0527

Gnomad SAS exome AF: 0.0736

Gnomad FIN exome AF: 0.0285

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.0780

GnomAD4 exome AF: 0.0701 AC: 102495 AN: 1461484 Hom.: 3910 Cov.: 31 AF XY: 0.0709 AC XY: 51581 AN XY: 727070

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.0996

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0320

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.0319

Gnomad4 NFE exome AF: 0.0723

Gnomad4 OTH exome AF: 0.0719

GnomAD4 genome AF: 0.0591 AC: 9003 AN: 152242 Hom.: 339 Cov.: 32 AF XY: 0.0594 AC XY: 4419 AN XY: 74434

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.0734

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0758 Hom.: 354

Bravo AF: 0.0627

TwinsUK AF: 0.0774 AC: 287

ALSPAC AF: 0.0625 AC: 241

ESP6500AA AF: 0.0233 AC: 87

ESP6500EA AF: 0.0706 AC: 580

ExAC AF: 0.0694 AC: 8389

Asia WGS AF: 0.0910 AC: 316 AN: 3478

EpiCase AF: 0.0797

EpiControl AF: 0.0838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.9	H;.;H
MutationTaster	Benign	0.21	P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.23
MutPred		0.29		Loss of glycosylation at S380 (P = 0.1166);.;Loss of glycosylation at S380 (P = 0.1166);
MPC		0.24
ClinPred		0.11	T
GERP RS		2.8
Varity_R		0.29
gMVP		0.74

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: rs35923425; hg19: chr3-169569432;