4-51995079-G-C

Variant names:

• chr4-51995079-G-C
• rs534526166
• NM_001024611.3:c.1943C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024611.3(LRRC66):​c.1943C>G​(p.Ala648Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC66 NM_001024611.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840
• Publications: 0 publications found

Genes affected

LRRC66 (HGNC:34299): (leucine rich repeat containing 66) This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03309998).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024611.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC66	NM_001024611.3	MANE Select	c.1943C>G	p.Ala648Gly	missense	Exon 5 of 5	NP_001019782.1	Q68CR7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC66	ENST00000682860.1	MANE Select	c.1943C>G	p.Ala648Gly	missense	Exon 5 of 5	ENSP00000508002.1	Q68CR7
	LRRC66	ENST00000343457.3	TSL:1	c.1943C>G	p.Ala648Gly	missense	Exon 4 of 4	ENSP00000341944.3	Q68CR7
	LRRC66	ENST00000893847.1		c.1943C>G	p.Ala648Gly	missense	Exon 5 of 5	ENSP00000563906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.53
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.084
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.023
Sift	Benign	0.20	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.13		Gain of glycosylation at Y653 (P = 0.0011)
MVP		0.030
MPC		0.026
ClinPred		0.058	T
GERP RS		-1.5
Varity_R		0.039
gMVP		0.017
Mutation Taster		=98/2	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: rs534526166; hg19: chr4-52861245;