Genetic Variant CRYBG2:p.Gln1579Glu (chr1-26324154-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001039775.4(CRYBG2):c.4735C>G(p.Gln1579Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000195 in 1,613,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CRYBG2
NM_001039775.4 missense, splice_region

Scores

Splicing: ADA: 0.9778

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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]

CRYBG2 links:

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=0.2603033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG2	NM_001039775.4 link	c.4735C>G	p.Gln1579Glu	missense_variant, splice_region_variant	Exon 18 of 20	ENST00000308182.10	NP_001034864.2	Q8N1P7Q9NWG5
CRYBG2	XM_011541673.3 link	c.4906C>G	p.Gln1636Glu	missense_variant, splice_region_variant	Exon 18 of 20		XP_011539975.1
CRYBG2	XM_005245918.3 link	c.4735C>G	p.Gln1579Glu	missense_variant, splice_region_variant	Exon 18 of 20		XP_005245975.1	Q8N1P7
CRYBG2	XM_011541672.2 link	c.4699C>G	p.Gln1567Glu	missense_variant, splice_region_variant	Exon 17 of 19		XP_011539974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRYBG2	ENST00000308182.10 link	c.4735C>G	p.Gln1579Glu	missense_variant, splice_region_variant	Exon 18 of 20	5	NM_001039775.4	ENSP00000310435.6	Q8N1P7
CRYBG2	ENST00000475866.3 link	c.5707C>G	p.Gln1903Glu	missense_variant, splice_region_variant	Exon 20 of 22	4		ENSP00000428746.2	E7ET48
CRYBG2	ENST00000374208.1 link	n.213C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	5
CRYBG2	ENST00000374211.5 link	n.349C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250444

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135386

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1460976

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

152

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000188

Gnomad4 NFE exome

AF:

0.000268

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000126

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4735C>G (p.Q1579E) alteration is located in exon 18 (coding exon 17) of the AIM1L gene. This alteration results from a C to G substitution at nucleotide position 4735, causing the glutamine (Q) at amino acid position 1579 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.77

PrimateAI

Benign

0.42

REVEL

Benign

0.19

Sift4G

Uncertain

0.012

.;D

Vest4

0.55

MVP

0.67

ClinPred

0.41

GERP RS

5.5

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Benign

0.71

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over