rs783396

chr6-106539495-A-Cchr6-106539495-A-Gchr6-106539495-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371242.2(CRYBG1):c.4811A>C(p.Glu1604Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 1,613,588 control chromosomes in the GnomAD database, including 697,806 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.93 (65927 hom., cov: 31)
  • Exomes 𝑓: 0.93 (631879 hom.)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.657758E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG1	NM_001371242.2	c.4811A>C	p.Glu1604Ala	missense_variant	9/22	ENST00000633556.3
CRYBG1	NM_001624.4	c.3587A>C	p.Glu1196Ala	missense_variant	7/20
CRYBG1	XM_047418270.1	c.4889A>C	p.Glu1630Ala	missense_variant	10/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3	c.4811A>C	p.Glu1604Ala	missense_variant	9/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141511 AN: 152136 Hom.: 65870 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.916

GnomAD3 exomes AF: 0.931 AC: 233875 AN: 251108 Hom.: 108967 AF XY: 0.933 AC XY: 126593 AN XY: 135746

Gnomad AFR exome AF: 0.935

Gnomad AMR exome AF: 0.922

Gnomad ASJ exome AF: 0.909

Gnomad EAS exome AF: 0.943

Gnomad SAS exome AF: 0.960

Gnomad FIN exome AF: 0.930

Gnomad NFE exome AF: 0.927

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.930 AC: 1358777 AN: 1461334 Hom.: 631879 Cov.: 45 AF XY: 0.931 AC XY: 676654 AN XY: 726978

Gnomad4 AFR exome AF: 0.937

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.912

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.960

Gnomad4 FIN exome AF: 0.932

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.926

GnomAD4 genome AF: 0.930 AC: 141627 AN: 152254 Hom.: 65927 Cov.: 31 AF XY: 0.931 AC XY: 69288 AN XY: 74446

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.916

Alfa AF: 0.926 Hom.: 161018

Bravo AF: 0.929

TwinsUK AF: 0.923 AC: 3421

ALSPAC AF: 0.939 AC: 3618

ESP6500AA AF: 0.939 AC: 4139

ESP6500EA AF: 0.923 AC: 7939

ExAC AF: 0.932 AC: 113216

Asia WGS AF: 0.949 AC: 3302 AN: 3478

EpiCase AF: 0.924

EpiControl AF: 0.916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	14
Dann	Benign	0.79
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.093	T;T
MetaRNN	Benign	5.7e-7	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	P
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.064	T;T
Polyphen		0.0	.;B
Vest4		0.052
MPC		0.089
ClinPred		0.026	T
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs783396; hg19: chr6-106987370;