chr5-191773-C-T

Variant names:

• chr5-191773-C-T
• rs1468365559
• NM_001080478.3:c.235C>T

Variant summary

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

The NM_001080478.3(LRRC14B):​c.235C>T​(p.Arg79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,542,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R79H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20164752).

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.235C>T	p.Arg79Cys	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.235C>T	p.Arg79Cys	missense	Exon 1 of 2	ENSP00000327675.3	A6NHZ5

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 140118 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1390430 Hom.: 0 Cov.: 31 AF XY: 0.0000102 AC XY: 7 AN XY: 685628

African (AFR) AF: 0.0000317 AC: 1 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 35808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35760

South Asian (SAS) AF: 0.00 AC: 0 AN: 79284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1077754

Other (OTH) AF: 0.0000347 AC: 2 AN: 57718

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.21
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.098	T
Sift4G	Benign	0.068	T
Polyphen		0.27	B
Vest4		0.27
MutPred		0.43		Loss of disorder (P = 0.0418)
MVP		0.22
MPC		0.29
ClinPred		0.52	D
GERP RS		3.2
PromoterAI		-0.0070	Neutral
Varity_R		0.097
gMVP		0.41
Mutation Taster		=91/9	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: rs1468365559; hg19: chr5-191888;