7-150330825-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142928.2(LRRC61):​c.-145+4815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,609,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LRRC61
NM_001142928.2 intron

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.60

Publications

0 publications found
Variant links:
Genes affected
LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
ZBED10P (HGNC:21720): (zinc finger BED-type containing 10, pseudogene)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044073075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC61NM_001142928.2 linkc.-145+4815G>A intron_variant Intron 2 of 2 ENST00000359623.9 NP_001136400.1 Q9BV99A0A090N7W5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC61ENST00000359623.9 linkc.-145+4815G>A intron_variant Intron 2 of 2 2 NM_001142928.2 ENSP00000352642.4 Q9BV99

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000122
AC:
3
AN:
245122
AF XY:
0.0000150
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000824
AC:
12
AN:
1457188
Hom.:
0
Cov.:
31
AF XY:
0.00000552
AC XY:
4
AN XY:
724290
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33348
American (AMR)
AF:
0.00
AC:
0
AN:
44512
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25984
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39620
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86138
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52442
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
0.00000811
AC:
9
AN:
1109252
Other (OTH)
AF:
0.0000333
AC:
2
AN:
60144
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41456
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000583
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 04, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.421G>A (p.G141R) alteration is located in exon 1 (coding exon 1) of the ZBED6CL gene. This alteration results from a G to A substitution at nucleotide position 421, causing the glycine (G) at amino acid position 141 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.084
DANN
Benign
0.51
DEOGEN2
Benign
0.0077
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PhyloP100
-2.6
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.0060
Sift
Benign
0.47
T
Sift4G
Benign
0.79
T
Polyphen
0.012
B
Vest4
0.051
MutPred
0.28
Gain of MoRF binding (P = 0.0105);
MVP
0.030
MPC
0.067
ClinPred
0.030
T
GERP RS
-6.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.045
gMVP
0.16

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

Other links and lift over

dbSNP: rs1288901155; hg19: chr7-150027914; API