Variant 3-97881206-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_153605.4(CRYBG3):c.7139A>G(p.Lys2380Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,603,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

CRYBG3
NM_153605.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

CRYBG3 (HGNC:34427): (crystallin beta-gamma domain containing 3) Enables protein kinase A binding activity. Predicted to be involved in lens development in camera-type eye and visual perception. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00839445).

BP6

Variant 3-97881206-A-G is Benign according to our data. Variant chr3-97881206-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 743355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG3	NM_153605.4 linkuse as main transcript	c.7139A>G	p.Lys2380Arg	missense_variant	7/22	ENST00000389622.7	NP_705833.3	Q68DQ2-3
CRYBG3	XM_005247117.5 linkuse as main transcript	c.6266A>G	p.Lys2089Arg	missense_variant	6/21		XP_005247174.1
CRYBG3	XM_047447439.1 linkuse as main transcript	c.7139A>G	p.Lys2380Arg	missense_variant	7/11		XP_047303395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG3	ENST00000389622.7 linkuse as main transcript	c.7139A>G	p.Lys2380Arg	missense_variant	7/22	5	NM_153605.4	ENSP00000374273.3		Q68DQ2-3

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000154

AC:

AN:

240410

Hom.:

AF XY:

0.0000843

AC XY:

AN XY:

130420

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.0000311

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:

0.0000593

AC:

AN:

1451300

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

721722

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.0000932

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:

0.000250

GnomAD4 genome

AF:

0.000630

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.000131

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:

0.00103

Hom.:

Bravo

AF:

0.000854

ESP6500AA

AF:

0.00220

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000224

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.12

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0084

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.45

Sift4G

Benign

0.31

Vest4

0.096

MVP

0.36

ClinPred

0.022

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.040

gMVP

0.67

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.

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