9-136763873-G-A

Position:

• chr9-136763873-G-A

Variant summary

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

The ENST00000316144.6(LCN15):​c.233C>T​(p.Pro78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,613,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: LCN15 ENST00000316144.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100

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=0.043924272).
• BP6: Variant 9-136763873-G-A is Benign according to our data. Variant chr9-136763873-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3118119.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.233C>T	p.Pro78Leu	missense_variant	2/7	ENST00000316144.6	NP_976222.1
LCN15	XM_011518672.2	c.104C>T	p.Pro35Leu	missense_variant	2/7		XP_011516974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCN15	ENST00000316144.6	c.233C>T	p.Pro78Leu	missense_variant	2/7	1	NM_203347.2	ENSP00000313833.5
LCN15	ENST00000482511.1	n.2383C>T		non_coding_transcript_exon_variant	1/6	1
LCN15	ENST00000495223.1	n.165C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000299 AC: 75 AN: 250796 Hom.: 0 AF XY: 0.000302 AC XY: 41 AN XY: 135602

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000353

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000446 AC: 652 AN: 1461244 Hom.: 1 Cov.: 33 AF XY: 0.000448 AC XY: 326 AN XY: 726920

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000693

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.0000567

Gnomad4 NFE exome AF: 0.000495

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74450

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000311 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000305 AC: 37

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

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

Jul 26, 2021

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	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.38
MVP		0.085
MPC		0.19
ClinPred		0.086	T
GERP RS		0.61
Varity_R		0.48
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs373629083; hg19: chr9-139658325;