9-135523884-G-A

Variant names:

• chr9-135523884-G-A
• rs117161567
• NM_002297.4:c.297G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002297.4(LCN1):​c.297G>A​(p.Gly99Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,613,572 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (53 hom.)
• Consequence: LCN1 NM_002297.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.565

Genes affected

LCN1 (HGNC:6525): (lipocalin 1) This gene encodes a member of the lipocalin family of small secretory proteins. Lipocalins are extracellular transport proteins that bind to a variety of hydrophobic ligands. The encoded protein is the primary lipid binding protein in tears and is overproduced in response to multiple stimuli including infection and stress. The encoded protein may be a marker for chromosome aneuploidy as well as an autoantigen in Sjogren's syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and two pseudogenes of this gene are also located on the long arm of chromosome 9. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-135523884-G-A is Benign according to our data. Variant chr9-135523884-G-A is described in ClinVar as [Benign]. Clinvar id is 711320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.565 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCN1	NM_002297.4	c.297G>A	p.Gly99Gly	synonymous_variant	Exon 4 of 7	ENST00000371781.4	NP_002288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCN1	ENST00000371781.4	c.297G>A	p.Gly99Gly	synonymous_variant	Exon 4 of 7	1	NM_002297.4	ENSP00000360846.3
LCN1	ENST00000263598.6	c.297G>A	p.Gly99Gly	synonymous_variant	Exon 4 of 7	1		ENSP00000263598.2

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 805 AN: 152188 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00765

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.00528 AC: 1326 AN: 251302 AF XY: 0.00534

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00411

Gnomad NFE exome AF: 0.00792

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00729 AC: 10652 AN: 1461266 Hom.: 53 Cov.: 31 AF XY: 0.00717 AC XY: 5212 AN XY: 726954

Gnomad4 AFR exome AF: 0.00108 AC: 36 AN: 33476

Gnomad4 AMR exome AF: 0.00586 AC: 262 AN: 44704

Gnomad4 ASJ exome AF: 0.00421 AC: 110 AN: 26126

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39696

Gnomad4 SAS exome AF: 0.000835 AC: 72 AN: 86244

Gnomad4 FIN exome AF: 0.00390 AC: 208 AN: 53400

Gnomad4 NFE exome AF: 0.00856 AC: 9511 AN: 1111480

Gnomad4 Remaining exome AF: 0.00730 AC: 441 AN: 60376

GnomAD4 genome AF: 0.00529 AC: 805 AN: 152306 Hom.: 2 Cov.: 33 AF XY: 0.00522 AC XY: 389 AN XY: 74470

Gnomad4 AFR AF: 0.00188 AC: 0.00187699 AN: 0.00187699

Gnomad4 AMR AF: 0.00764 AC: 0.00764406 AN: 0.00764406

Gnomad4 ASJ AF: 0.00317 AC: 0.0031682 AN: 0.0031682

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000621 AC: 0.000621375 AN: 0.000621375

Gnomad4 FIN AF: 0.00414 AC: 0.00414391 AN: 0.00414391

Gnomad4 NFE AF: 0.00782 AC: 0.00782054 AN: 0.00782054

Gnomad4 OTH AF: 0.00853 AC: 0.00853081 AN: 0.00853081

Alfa AF: 0.00697 Hom.: 3

Bravo AF: 0.00566

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00818

EpiControl AF: 0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.62
DANN	Benign	0.74
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs117161567; hg19: chr9-138415730; COSMIC: COSV55018401;