rs764529033

Variant names:

• chr5-191689-C-T
• rs764529033
• NM_001080478.3:c.151C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-191689-C-T
• chr5-191689-C-A

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.151C>T​(p.Arg51Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000438 in 1,599,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R51G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• 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=0.15012476).

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.151C>T	p.Arg51Cys	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.151C>T	p.Arg51Cys	missense	Exon 1 of 2	ENSP00000327675.3	A6NHZ5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000915 AC: 2 AN: 218486 AF XY: 0.0000168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000315

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: 0.00000415 AC: 6 AN: 1447182 Hom.: 0 Cov.: 31 AF XY: 0.00000557 AC XY: 4 AN XY: 718634

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.0000233 AC: 1 AN: 42850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39004

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 84076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105722

Other (OTH) AF: 0.0000167 AC: 1 AN: 59800

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000624 Hom.: 0

ExAC AF: 0.00000831 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.14
Sift	Benign	0.050	D
Sift4G	Benign	0.10	T
Polyphen		0.0070	B
Vest4		0.22
MutPred		0.55		Gain of helix (P = 0.0696)
MVP		0.19
MPC		0.29
ClinPred		0.46	T
GERP RS		3.4
PromoterAI		0.068	Neutral
Varity_R		0.18
gMVP		0.26
Mutation Taster		=93/7	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: rs764529033; hg19: chr5-191804;