rs62273959

Positions:

• chr3-156852891-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001004316.3(LEKR1):​c.172G>A​(p.Val58Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,534,660 control chromosomes in the GnomAD database, including 1,580 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (117 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1463 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

Genes affected

LEKR1 (HGNC:33765): (leucine, glutamate and lysine rich 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014481544).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4844/152096) while in subpopulation NFE AF= 0.0476 (3232/67920). AF 95% confidence interval is 0.0462. There are 117 homozygotes in gnomad4. There are 2396 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 117 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3	c.172G>A	p.Val58Ile	missense_variant	3/13	ENST00000356539.9	NP_001004316.2
LEKR1	NM_001193283.2	c.172G>A	p.Val58Ile	missense_variant	3/5		NP_001180212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEKR1	ENST00000356539.9	c.172G>A	p.Val58Ile	missense_variant	3/13	5	NM_001004316.3	ENSP00000348936	P1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4846 AN: 151978 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0280 AC: 3965 AN: 141582 Hom.: 90 AF XY: 0.0275 AC XY: 2084 AN XY: 75740

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.0205

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00762

Gnomad FIN exome AF: 0.0738

Gnomad NFE exome AF: 0.0468

Gnomad OTH exome AF: 0.0252

GnomAD4 exome AF: 0.0435 AC: 60085 AN: 1382564 Hom.: 1463 Cov.: 30 AF XY: 0.0421 AC XY: 28750 AN XY: 682328

Gnomad4 AFR exome AF: 0.00657

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0000844

Gnomad4 SAS exome AF: 0.00786

Gnomad4 FIN exome AF: 0.0691

Gnomad4 NFE exome AF: 0.0498

Gnomad4 OTH exome AF: 0.0378

GnomAD4 genome AF: 0.0318 AC: 4844 AN: 152096 Hom.: 117 Cov.: 32 AF XY: 0.0322 AC XY: 2396 AN XY: 74340

Gnomad4 AFR AF: 0.00842

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00624

Gnomad4 FIN AF: 0.0764

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0424 Hom.: 245

Bravo AF: 0.0268

TwinsUK AF: 0.0507 AC: 188

ALSPAC AF: 0.0483 AC: 186

ESP6500AA AF: 0.00867 AC: 12

ESP6500EA AF: 0.0534 AC: 170

ExAC AF: 0.0214 AC: 425

Asia WGS AF: 0.00462 AC: 16 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.2
DANN	Uncertain	0.98
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.76	T;T;T;.;T;T
MetaRNN	Benign	0.0014	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.52	N;N;N;N;.;.
REVEL	Benign	0.12
Sift	Benign	0.31	T;T;T;T;.;.
Sift4G	Benign	0.30	T;T;T;T;T;.
Polyphen		0.021	.;.;.;B;B;.
Vest4		0.095
ClinPred		0.0063	T
GERP RS		1.6
gMVP		0.0090

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: rs62273959; hg19: chr3-156570680; COSMIC: COSV62963715; COSMIC: COSV62963715;