dbSNP rs183657850: LEKR1:p.Ala411Thr (chr3-157024787-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004316.3(LEKR1):c.1231G>A(p.Ala411Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,610,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

LEKR1
NM_001004316.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Publications

2 publications found

Variant links:

Genes affected

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

LEKR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011200368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004316.3. 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
	LEKR1	NM_001004316.3	MANE Select	c.1231G>A	p.Ala411Thr	missense	Exon 11 of 13	NP_001004316.2	J3KP02

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LEKR1	ENST00000356539.9	TSL:5 MANE Select	c.1231G>A	p.Ala411Thr	missense	Exon 11 of 13	ENSP00000348936.4	J3KP02
LEKR1	ENST00000470811.6	TSL:2	n.*709G>A		non_coding_transcript_exon	Exon 12 of 14	ENSP00000418214.2	A0A8I5FW65
LEKR1	ENST00000470811.6	TSL:2	n.*709G>A		3_prime_UTR	Exon 12 of 14	ENSP00000418214.2	A0A8I5FW65

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

248674

AF XY:

0.000112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00187

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000549

AC:

AN:

1458504

Hom.:

Cov.:

AF XY:

0.0000483

AC XY:

AN XY:

725370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

43956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00192

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111100

Other (OTH)

AF:

0.0000166

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.5

PhyloP100

2.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Benign

0.065

Sift

Benign

0.39

Sift4G

Benign

0.54

Polyphen

1.0

Vest4

0.19

MVP

0.13

ClinPred

0.20

GERP RS

4.5

Varity_R

0.078

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over