chr16-67375277-G-A

Variant names:

• chr16-67375277-G-A
• rs8052655
• NM_018296.6:c.1525G>A

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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 0.18 (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
• Publications: 28 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018296.6. 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
	LRRC36	NM_018296.6	MANE Select	c.1525G>A	p.Gly509Ser	missense	Exon 10 of 14	NP_060766.5
	LRRC36	NM_001161575.2		c.1162G>A	p.Gly388Ser	missense	Exon 7 of 11	NP_001155047.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC36	ENST00000329956.11	TSL:1 MANE Select	c.1525G>A	p.Gly509Ser	missense	Exon 10 of 14	ENSP00000329943.6
	LRRC36	ENST00000563189.5	TSL:1	c.1162G>A	p.Gly388Ser	missense	Exon 7 of 11	ENSP00000455103.1
	LRRC36	ENST00000565019.6	TSL:1	n.*246-38G>A		intron	N/A	ENSP00000464675.1

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

GnomAD2 exomes AF: 0.0793 AC: 19851 AN: 250348 AF XY: 0.0725

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 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

African (AFR) AF: 0.536 AC: 17896 AN: 33372

American (AMR) AF: 0.0577 AC: 2579 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 1732 AN: 26124

East Asian (EAS) AF: 0.00161 AC: 64 AN: 39696

South Asian (SAS) AF: 0.0777 AC: 6696 AN: 86226

European-Finnish (FIN) AF: 0.0419 AC: 2208 AN: 52734

Middle Eastern (MID) AF: 0.137 AC: 790 AN: 5766

European-Non Finnish (NFE) AF: 0.0437 AC: 48559 AN: 1111804

Other (OTH) AF: 0.0827 AC: 4991 AN: 60360

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

African (AFR) AF: 0.514 AC: 21130 AN: 41096

American (AMR) AF: 0.0939 AC: 1422 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.00409 AC: 21 AN: 5136

South Asian (SAS) AF: 0.0718 AC: 343 AN: 4776

European-Finnish (FIN) AF: 0.0377 AC: 386 AN: 10242

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2964 AN: 67812

Other (OTH) AF: 0.142 AC: 298 AN: 2100

Alfa AF: 0.0831 Hom.: 7490

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 v4.9

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
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.16
MPC		0.82
ClinPred		0.017	T
GERP RS		5.7
Varity_R		0.12
gMVP		0.36
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8052655; hg19: chr16-67409180; COSMIC: COSV52081215; COSMIC: COSV52081215;