chr4-51994413-G-C

Variant names:

• chr4-51994413-G-C
• rs746733449
• NM_001024611.3:c.2609C>G

Variant summary

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

The NM_001024611.3(LRRC66):​c.2609C>G​(p.Ala870Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A870V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC66 NM_001024611.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• 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: 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=0.10203943).

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.2609C>G	p.Ala870Gly	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.2609C>G	p.Ala870Gly	missense	Exon 5 of 5	ENSP00000508002.1	Q68CR7
	LRRC66	ENST00000343457.3	TSL:1	c.2609C>G	p.Ala870Gly	missense	Exon 4 of 4	ENSP00000341944.3	Q68CR7
	LRRC66	ENST00000893847.1		c.2609C>G	p.Ala870Gly	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.46
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.58
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.032
Sift	Benign	0.35	T
Sift4G	Benign	0.62	T
Polyphen		0.68	P
Vest4		0.085
MutPred		0.20		Loss of helix (P = 0.0123)
MVP		0.055
MPC		0.047
ClinPred		0.21	T
GERP RS		-3.9
Varity_R		0.037
gMVP		0.0069
Mutation Taster		=99/1	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: rs746733449; hg19: chr4-52860579;