Genetic Variant CRYBG1:p.Ala556Glu (chr6-106512784-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371242.2(CRYBG1):c.1667C>A(p.Ala556Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,579,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A556V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CRYBG1
NM_001371242.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

0 publications found

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:

ENSG00000300544 (HGNC:):

ENSG00000300544 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17753008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371242.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG1	NM_001371242.2	MANE Select	c.1667C>A	p.Ala556Glu	missense	Exon 3 of 22	NP_001358171.1	Q9Y4K1-3
	CRYBG1	NM_001624.4		c.443C>A	p.Ala148Glu	missense	Exon 1 of 20	NP_001615.2	Q9Y4K1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRYBG1	ENST00000633556.3	TSL:5 MANE Select	c.1667C>A	p.Ala556Glu	missense	Exon 3 of 22	ENSP00000488010.2	Q9Y4K1-3
CRYBG1	ENST00000651520.1		c.1508C>A	p.Ala503Glu	missense	Exon 2 of 2	ENSP00000499126.1	A0A494C1M5
ENSG00000300544	ENST00000772631.1		n.194G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

189028

AF XY:

0.00000968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427524

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32800

American (AMR)

AF:

0.0000248

AC:

AN:

40308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25312

East Asian (EAS)

AF:

0.0000262

AC:

AN:

38116

South Asian (SAS)

AF:

0.00

AC:

AN:

82416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49454

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094560

Other (OTH)

AF:

0.00

AC:

AN:

58948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.47

M_CAP

Benign

0.056

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.79

PhyloP100

1.2

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

REVEL

Benign

0.16

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.028

Polyphen

0.81

Vest4

0.30

MutPred

0.17

Gain of solvent accessibility (P = 0.0145)

MVP

0.71

MPC

0.33

ClinPred

0.51

GERP RS

4.5

Varity_R

0.29

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over