1-26322050-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039775.4(CRYBG2):​c.4904G>A​(p.Arg1635Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,606,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1635W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CRYBG2
NM_001039775.4 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.129
Variant links:
Genes affected
CRYBG2 (HGNC:17295): (crystallin beta-gamma domain containing 2) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.032063693).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRYBG2NM_001039775.4 linkc.4904G>A p.Arg1635Gln missense_variant Exon 20 of 20 ENST00000308182.10 NP_001034864.2 Q8N1P7Q9NWG5
CRYBG2XM_011541673.3 linkc.5075G>A p.Arg1692Gln missense_variant Exon 20 of 20 XP_011539975.1
CRYBG2XM_005245918.3 linkc.4904G>A p.Arg1635Gln missense_variant Exon 20 of 20 XP_005245975.1 Q8N1P7
CRYBG2XM_011541672.2 linkc.4868G>A p.Arg1623Gln missense_variant Exon 19 of 19 XP_011539974.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRYBG2ENST00000308182.10 linkc.4904G>A p.Arg1635Gln missense_variant Exon 20 of 20 5 NM_001039775.4 ENSP00000310435.6 Q8N1P7
CRYBG2ENST00000475866.3 linkc.5876G>A p.Arg1959Gln missense_variant Exon 22 of 22 4 ENSP00000428746.2 E7ET48
CRYBG2ENST00000374208.1 linkn.382G>A non_coding_transcript_exon_variant Exon 4 of 4 5
CRYBG2ENST00000374211.5 linkn.518G>A non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000360
AC:
9
AN:
249802
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134936
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000230
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1454016
Hom.:
0
Cov.:
29
AF XY:
0.0000319
AC XY:
23
AN XY:
721516
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000450
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000814
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0000722
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
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4904G>A (p.R1635Q) alteration is located in exon 20 (coding exon 19) of the AIM1L gene. This alteration results from a G to A substitution at nucleotide position 4904, causing the arginine (R) at amino acid position 1635 to be replaced by a glutamine (Q). 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
0.088
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Benign
0.88
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.032
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.22
T
REVEL
Benign
0.049
Sift4G
Benign
0.23
.;T
Vest4
0.11
MVP
0.26
ClinPred
0.065
T
GERP RS
1.9
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs147012844; hg19: chr1-26648541; API