10-93593803-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_006744.4(RBP4):​c.568+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,456,808 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

RBP4
NM_006744.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.238

Publications

0 publications found
Variant links:
Genes affected
RBP4 (HGNC:9922): (retinol binding protein 4) This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells. [provided by RefSeq, Jul 2008]
FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 10-93593803-G-A is Benign according to our data. Variant chr10-93593803-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3680584.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0000302 (44/1456808) while in subpopulation NFE AF = 0.0000396 (44/1110474). AF 95% confidence interval is 0.00003. There are 0 homozygotes in GnomAdExome4. There are 19 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBP4NM_006744.4 linkc.568+20C>T intron_variant Intron 5 of 5 ENST00000371464.8 NP_006735.2 P02753
RBP4NM_001323517.1 linkc.568+20C>T intron_variant Intron 5 of 5 NP_001310446.1 P02753
RBP4NM_001323518.2 linkc.562+20C>T intron_variant Intron 5 of 5 NP_001310447.1 P02753Q5VY30

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBP4ENST00000371464.8 linkc.568+20C>T intron_variant Intron 5 of 5 1 NM_006744.4 ENSP00000360519.3 P02753
FFAR4ENST00000604414.1 linkc.697-10271G>A intron_variant Intron 2 of 2 3 ENSP00000474477.1 S4R3L2
RBP4ENST00000371467.5 linkc.568+20C>T intron_variant Intron 5 of 5 5 ENSP00000360522.1 P02753
RBP4ENST00000371469.2 linkc.562+20C>T intron_variant Intron 5 of 5 5 ENSP00000360524.2 Q5VY30

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249670
AF XY:
0.00000740
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:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000302
AC:
44
AN:
1456808
Hom.:
0
Cov.:
32
AF XY:
0.0000262
AC XY:
19
AN XY:
724908
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33388
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26118
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86134
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51988
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4162
European-Non Finnish (NFE)
AF:
0.0000396
AC:
44
AN:
1110474
Other (OTH)
AF:
0.00
AC:
0
AN:
60146
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
3
6
10
13
16
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
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.82
CADD
Benign
3.9
DANN
Benign
0.55
PhyloP100
-0.24
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

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: rs764165063; hg19: chr10-95353560; API