5-192028-G-A

Variant names:

• chr5-192028-G-A
• rs753789830
• NM_001080478.3:c.490G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080478.3(LRRC14B):​c.490G>A​(p.Val164Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,386,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V164L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34
• Publications: 0 publications found

Genes affected

LRRC14B (HGNC:37268): (leucine rich repeat containing 14B) The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28515798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080478.3. 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
	LRRC14B	NM_001080478.3	MANE Select	c.490G>A	p.Val164Ile	missense	Exon 1 of 2	NP_001073947.1	A6NHZ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14B	ENST00000328278.4	TSL:1 MANE Select	c.490G>A	p.Val164Ile	missense	Exon 1 of 2	ENSP00000327675.3	A6NHZ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1386420 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 2 AN XY: 684510

African (AFR) AF: 0.00 AC: 0 AN: 31764

American (AMR) AF: 0.00 AC: 0 AN: 36140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 36002

South Asian (SAS) AF: 0.00 AC: 0 AN: 79438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079930

Other (OTH) AF: 0.00 AC: 0 AN: 57972

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.3
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.17
Sift	Benign	0.076	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.37		Loss of catalytic residue at V164 (P = 0.0446)
MVP		0.25
MPC		0.25
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.052
gMVP		0.32
Mutation Taster		=86/14	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: rs753789830; hg19: chr5-192143;