chr4-109828059-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006583.5(RRH):ā€‹c.32A>Gā€‹(p.Asp11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

RRH
NM_006583.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48
Variant links:
Genes affected
RRH (HGNC:10450): (retinal pigment epithelium-derived rhodopsin homolog) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes opsin 5 and retinal G protein coupled receptor. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07840121).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRHNM_006583.5 linkuse as main transcriptc.32A>G p.Asp11Gly missense_variant 1/7 ENST00000317735.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRHENST00000317735.7 linkuse as main transcriptc.32A>G p.Asp11Gly missense_variant 1/71 NM_006583.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251270
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460186
Hom.:
0
Cov.:
29
AF XY:
0.00000413
AC XY:
3
AN XY:
726450
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 06, 2021The c.32A>G (p.D11G) alteration is located in exon 1 (coding exon 1) of the RRH gene. This alteration results from a A to G substitution at nucleotide position 32, causing the aspartic acid (D) at amino acid position 11 to be replaced by a glycine (G). 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
0.078
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.029
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.11
Sift
Benign
0.26
T
Sift4G
Benign
0.37
T
Polyphen
0.0010
B
Vest4
0.13
MVP
0.68
MPC
0.028
ClinPred
0.039
T
GERP RS
-0.17
Varity_R
0.087
gMVP
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370590600; hg19: chr4-110749215; API