Variant 3-97876913-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153605.4(CRYBG3):c.5719A>G(p.Thr1907Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,453,600 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 61 hom. )

Consequence

CRYBG3
NM_153605.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.792

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062221587).

BP6

Variant 3-97876913-A-G is Benign according to our data. Variant chr3-97876913-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3387997.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG3	NM_153605.4 linkuse as main transcript	c.5719A>G	p.Thr1907Ala	missense_variant	4/22	ENST00000389622.7	NP_705833.3	Q68DQ2-3
CRYBG3	XM_005247117.5 linkuse as main transcript	c.4846A>G	p.Thr1616Ala	missense_variant	3/21		XP_005247174.1
CRYBG3	XM_047447439.1 linkuse as main transcript	c.5719A>G	p.Thr1907Ala	missense_variant	4/11		XP_047303395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG3	ENST00000389622.7 linkuse as main transcript	c.5719A>G	p.Thr1907Ala	missense_variant	4/22	5	NM_153605.4	ENSP00000374273.3		Q68DQ2-3

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1079

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0149

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.00794

AC:

10332

AN:

1301300

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

4909

AN XY:

630524

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00343

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00836

Gnomad4 OTH exome

AF:

0.00790

GnomAD4 genome

AF:

0.00709

AC:

1080

AN:

152300

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

529

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0149

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00584

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00675

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

CRYBG3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.29

DANN

Benign

0.74

DEOGEN2

Benign

0.0019

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0062

Sift4G

Benign

0.15

Vest4

0.032

MVP

0.66

GERP RS

-1.8

Varity_R

0.086

gMVP

0.054

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