Variant 6-106512814-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001371242.2(CRYBG1):c.1697C>T(p.Ala566Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,574,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

CRYBG1
NM_001371242.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

Variant links:

Genes affected

CRYBG1 (HGNC:356): (crystallin beta-gamma domain containing 1) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008682668).

BP6

Variant 6-106512814-C-T is Benign according to our data. Variant chr6-106512814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3269673.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRYBG1	NM_001371242.2 linkuse as main transcript	c.1697C>T	p.Ala566Val	missense_variant	3/22	ENST00000633556.3
CRYBG1	NM_001624.4 linkuse as main transcript	c.473C>T	p.Ala158Val	missense_variant	1/20
CRYBG1	XM_047418270.1 linkuse as main transcript	c.1775C>T	p.Ala592Val	missense_variant	4/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3 linkuse as main transcript	c.1697C>T	p.Ala566Val	missense_variant	3/22	5	NM_001371242.2	P1
CRYBG1	ENST00000651520.1 linkuse as main transcript	c.1538C>T	p.Ala513Val	missense_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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:

0.0000443

AC:

AN:

180690

Hom.:

AF XY:

0.0000204

AC XY:

AN XY:

98198

show subpopulations

Gnomad AFR exome

AF:

0.000737

Gnomad AMR exome

AF:

0.0000358

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:

0.00000914

AC:

AN:

1422270

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

703660

show subpopulations

Gnomad4 AFR exome

AF:

0.000337

Gnomad4 AMR exome

AF:

0.0000254

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:

0.0000170

GnomAD4 genome

AF:

0.000112

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000410

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:

0.0000831

ESP6500AA

AF:

0.000504

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000338

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.5

DANN

Benign

0.85

DEOGEN2

Benign

0.0030

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.92

.;N

REVEL

Benign

0.065

Sift

Benign

1.0

.;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

.;B

Vest4

0.043

MVP

0.40

MPC

0.081

ClinPred

0.013

GERP RS

1.2

Varity_R

0.017

gMVP

0.14

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