chr8-144519798-T-G

Variant names:

• chr8-144519798-T-G
• rs2721172
• NM_014665.4:c.73T>G

Variant summary

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

The NM_014665.4(LRRC14):​c.73T>G​(p.Leu25Val) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 14 publications found

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

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=0.10210395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014665.4. 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
	LRRC14	NM_014665.4	MANE Select	c.73T>G	p.Leu25Val	missense	Exon 2 of 4	NP_055480.1
	LRRC14	NM_001272036.2		c.73T>G	p.Leu25Val	missense	Exon 3 of 5	NP_001258965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.73T>G	p.Leu25Val	missense	Exon 2 of 4	ENSP00000292524.1
	LRRC14	ENST00000529022.5	TSL:1	c.73T>G	p.Leu25Val	missense	Exon 3 of 5	ENSP00000434768.1
	LRRC14	ENST00000527730.1	TSL:2	c.73T>G	p.Leu25Val	missense	Exon 2 of 3	ENSP00000436452.1

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.22
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.022
Sift	Benign	0.47	T
Sift4G	Benign	0.16	T
Polyphen		0.40	B
Vest4		0.074
MutPred		0.38		Loss of glycosylation at P24 (P = 0.0809)
MVP		0.26
MPC		0.62
ClinPred		0.24	T
GERP RS		3.7
Varity_R		0.046
gMVP		0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2721172; hg19: chr8-145745182;