rs8052655

Positions:

• chr16-67375277-G-A

Variant summary

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

The NM_018296.6(LRRC36):​c.1525G>A​(p.Gly509Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 1,611,768 control chromosomes in the GnomAD database, including 12,601 homozygotes. In-silico tool predicts 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 0.18 (5712 hom., cov: 31)
  • Exomes 𝑓: 0.059 (6889 hom.)
• Consequence: LRRC36 NM_018296.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

Genes affected

LRRC36 (HGNC:25615): (leucine rich repeat containing 36)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011099577).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC36	NM_018296.6	c.1525G>A	p.Gly509Ser	missense_variant	10/14	ENST00000329956.11	NP_060766.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC36	ENST00000329956.11	c.1525G>A	p.Gly509Ser	missense_variant	10/14	1	NM_018296.6	ENSP00000329943.6

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26808 AN: 150874 Hom.: 5682 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.00408

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.0793 AC: 19851 AN: 250348 Hom.: 2588 AF XY: 0.0725 AC XY: 9816 AN XY: 135420

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.0543

Gnomad ASJ exome AF: 0.0646

Gnomad EAS exome AF: 0.00246

Gnomad SAS exome AF: 0.0821

Gnomad FIN exome AF: 0.0378

Gnomad NFE exome AF: 0.0455

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0585 AC: 85515 AN: 1460784 Hom.: 6889 Cov.: 33 AF XY: 0.0576 AC XY: 41895 AN XY: 726772

Gnomad4 AFR exome AF: 0.536

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.0663

Gnomad4 EAS exome AF: 0.00161

Gnomad4 SAS exome AF: 0.0777

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.178 AC: 26880 AN: 150984 Hom.: 5712 Cov.: 31 AF XY: 0.173 AC XY: 12753 AN XY: 73632

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.0939

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.00409

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0638 Hom.: 1825

Bravo AF: 0.194

TwinsUK AF: 0.0491 AC: 182

ALSPAC AF: 0.0446 AC: 172

ESP6500AA AF: 0.503 AC: 2213

ESP6500EA AF: 0.0428 AC: 368

ExAC AF: 0.0898 AC: 10897

Asia WGS AF: 0.0740 AC: 259 AN: 3478

EpiCase AF: 0.0462

EpiControl AF: 0.0508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.66	N;N
REVEL	Benign	0.17
Sift	Benign	0.26	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		1.0	D;D
Vest4		0.16
MPC		0.82
ClinPred		0.017	T
GERP RS		5.7
Varity_R		0.12
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8052655; hg19: chr16-67409180; COSMIC: COSV52081215; COSMIC: COSV52081215;