Variant 6-106512507-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371242.2(CRYBG1):c.1390G>C(p.Glu464Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,611,046 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

CRYBG1
NM_001371242.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.008964717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRYBG1	NM_001371242.2 linkuse as main transcript	c.1390G>C	p.Glu464Gln	missense_variant	3/22	ENST00000633556.3
CRYBG1	NM_001624.4 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	1/20
CRYBG1	XM_047418270.1 linkuse as main transcript	c.1468G>C	p.Glu490Gln	missense_variant	4/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3 linkuse as main transcript	c.1390G>C	p.Glu464Gln	missense_variant	3/22	5	NM_001371242.2	P1
CRYBG1	ENST00000651520.1 linkuse as main transcript	c.1231G>C	p.Glu411Gln	missense_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00425

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000562

AC:

135

AN:

240344

Hom.:

AF XY:

0.000524

AC XY:

AN XY:

131784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00178

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1458716

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

208

AN XY:

725524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00575

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000479

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00426

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.000771

ExAC

AF:

0.000306

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.166G>C (p.E56Q) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a G to C substitution at nucleotide position 166, causing the glutamic acid (E) at amino acid position 56 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

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.080

MetaRNN

Benign

0.0090

T;T

MetaSVM

Uncertain

-0.12

MutationTaster

Benign

0.86

PrimateAI

Uncertain

0.77

Sift4G

Benign

0.20

T;D

Polyphen

0.99

.;D

Vest4

0.13

MVP

0.76

MPC

0.38

ClinPred

0.066

GERP RS

2.9

Varity_R

0.14

gMVP

0.37

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