9-136762230-G-C

Position:

• chr9-136762230-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_203347.2(LCN15):​c.478C>G​(p.Leu160Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LCN15 NM_203347.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

Genes affected

LCN15 (HGNC:33777): (lipocalin 15) Predicted to enable small molecule binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LCN15 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041561127).
• BP6: Variant 9-136762230-G-C is Benign according to our data. Variant chr9-136762230-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3118123.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCN15	NM_203347.2	c.478C>G	p.Leu160Val	missense_variant	5/7	ENST00000316144.6	NP_976222.1
LCN15	XM_011518672.2	c.349C>G	p.Leu117Val	missense_variant	5/7		XP_011516974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN15	ENST00000316144.6	c.478C>G	p.Leu160Val	missense_variant	5/7	1	NM_203347.2	ENSP00000313833.5
LCN15	ENST00000482511.1	n.2628C>G		non_coding_transcript_exon_variant	4/6	1
LCN15	ENST00000495223.1	n.208+1514C>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.60
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.94	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.047
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MutPred		0.55		Gain of methylation at K164 (P = 0.0611);
MVP		0.085
MPC		0.16
ClinPred		0.054	T
GERP RS		0.89
Varity_R		0.12
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139656682;