chr9-135522118-G-A

Variant names:

• chr9-135522118-G-A
• rs141659926
• NM_002297.4:c.162G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002297.4(LCN1):​c.162G>A​(p.Val54Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,598,656 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (2 hom.)
• Consequence: LCN1 NM_002297.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.783
• Publications: 0 publications found

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-135522118-G-A is Benign according to our data. Variant chr9-135522118-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2659710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.783 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002297.4. 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
	LCN1	NM_002297.4	MANE Select	c.162G>A	p.Val54Val	synonymous	Exon 2 of 7	NP_002288.1	P31025
	LCN1	NM_001252618.2		c.162G>A	p.Val54Val	synonymous	Exon 2 of 7	NP_001239547.1
	LCN1	NM_001252619.2		c.162G>A	p.Val54Val	synonymous	Exon 2 of 7	NP_001239548.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCN1	ENST00000371781.4	TSL:1 MANE Select	c.162G>A	p.Val54Val	synonymous	Exon 2 of 7	ENSP00000360846.3	P31025
	LCN1	ENST00000263598.6	TSL:1	c.162G>A	p.Val54Val	synonymous	Exon 2 of 7	ENSP00000263598.2	P31025

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152148 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00118 AC: 215 AN: 182862 AF XY: 0.00132

Gnomad AFR exome AF: 0.000292

Gnomad AMR exome AF: 0.000814

Gnomad ASJ exome AF: 0.00521

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.00195 AC: 2818 AN: 1446390 Hom.: 2 Cov.: 32 AF XY: 0.00191 AC XY: 1371 AN XY: 718286

African (AFR) AF: 0.000424 AC: 14 AN: 33028

American (AMR) AF: 0.000756 AC: 32 AN: 42340

Ashkenazi Jewish (ASJ) AF: 0.00497 AC: 128 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38814

South Asian (SAS) AF: 0.00 AC: 0 AN: 83896

European-Finnish (FIN) AF: 0.0000381 AC: 2 AN: 52456

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5596

European-Non Finnish (NFE) AF: 0.00227 AC: 2510 AN: 1104780

Other (OTH) AF: 0.00219 AC: 131 AN: 59704

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152266 Hom.: 1 Cov.: 33 AF XY: 0.00121 AC XY: 90 AN XY: 74448

African (AFR) AF: 0.000481 AC: 20 AN: 41540

American (AMR) AF: 0.00242 AC: 37 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68016

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.00145

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.53
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs141659926; hg19: chr9-138413964;