rs2721172

chr8-144519798-T-Achr8-144519798-T-Cchr8-144519798-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014665.4(LRRC14):c.73T>A(p.Leu25Met) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L25L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 36)
• Consequence: LRRC14 NM_014665.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16797265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14	NM_014665.4	c.73T>A	p.Leu25Met	missense_variant	2/4	ENST00000292524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14	ENST00000292524.6	c.73T>A	p.Leu25Met	missense_variant	2/4	1	NM_014665.4	P1

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	17
Dann	Uncertain	1.0
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.63	T;.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.26	N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.26	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.97	.;D;D;.;.
Vest4		0.23
MutPred		0.38		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.40
MPC		1.1
ClinPred		0.38	T
GERP RS		3.7
Varity_R		0.071
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2721172; hg19: chr8-145745182;