NM_001080478.3:c.569C>T

Variant names:

• chr5-192107-C-T
• rs1028644702
• NM_001080478.3:c.569C>T

Variant summary

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

The NM_001080478.3(LRRC14B):​c.569C>T​(p.Ser190Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000426 in 1,407,612 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. S190W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: LRRC14B NM_001080478.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 1 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=0.3041278).

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.569C>T	p.Ser190Leu	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.569C>T	p.Ser190Leu	missense	Exon 1 of 2	ENSP00000327675.3	A6NHZ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000614 AC: 1 AN: 162758 AF XY: 0.0000112

Gnomad AFR exome AF: 0.000121

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: 0.00000426 AC: 6 AN: 1407612 Hom.: 0 Cov.: 32 AF XY: 0.00000575 AC XY: 4 AN XY: 695662

African (AFR) AF: 0.0000310 AC: 1 AN: 32292

American (AMR) AF: 0.00 AC: 0 AN: 38818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25298

East Asian (EAS) AF: 0.00 AC: 0 AN: 36866

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1087518

Other (OTH) AF: 0.00 AC: 0 AN: 58386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.042
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.15
Sift	Benign	0.065	T
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.41
MutPred		0.48		Loss of disorder (P = 0.0159)
MVP		0.21
MPC		0.45
ClinPred		0.70	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.41
Mutation Taster		=95/5	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: rs1028644702; hg19: chr5-192222; COSMIC: COSV52045226; COSMIC: COSV52045226;