rs1402935845

Variant names:

• chr7-16566345-C-G
• rs1402935845
• NM_001195280.2:c.460C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-16566345-C-G
• chr7-16566345-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195280.2(LRRC72):​c.460C>G​(p.Leu154Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 1,546,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: LRRC72 NM_001195280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.428
• Publications: 0 publications found

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09325135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.460C>G	p.Leu154Val	missense_variant	Exon 6 of 9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.460C>G	p.Leu154Val	missense_variant	Exon 6 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.460C>G	p.Leu154Val	missense_variant	Exon 6 of 9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000343 AC: 5 AN: 145878 AF XY: 0.0000509

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000738

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000552 AC: 77 AN: 1393992 Hom.: 0 Cov.: 29 AF XY: 0.0000524 AC XY: 36 AN XY: 687342

African (AFR) AF: 0.00 AC: 0 AN: 31450

American (AMR) AF: 0.0000570 AC: 2 AN: 35074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 35576

South Asian (SAS) AF: 0.00 AC: 0 AN: 77858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.0000668 AC: 72 AN: 1077332

Other (OTH) AF: 0.0000519 AC: 3 AN: 57842

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74300

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.460C>G (p.L154V) alteration is located in exon 6 (coding exon 6) of the LRRC72 gene. This alteration results from a C to G substitution at nucleotide position 460, causing the leucine (L) at amino acid position 154 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.94
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.62	N
PhyloP100		-0.43
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.054
Sift	Benign	0.52	T
Sift4G	Benign	0.56	T
Vest4		0.087
MVP		0.21
ClinPred		0.030	T
GERP RS		-4.1
Varity_R		0.039
gMVP		0.091
Mutation Taster		=93/7	polymorphism

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: rs1402935845; hg19: chr7-16605970;