rs783396

Variant names:

• chr6-106539495-A-C
• rs783396
• NM_001371242.2:c.4811A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-106539495-A-C
• chr6-106539495-A-G
• chr6-106539495-A-T

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• Publications: 44 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.4811A>C	p.Glu1604Ala	missense_variant	Exon 9 of 22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.3587A>C	p.Glu1196Ala	missense_variant	Exon 7 of 20		NP_001615.2
CRYBG1	XM_047418270.1	c.4889A>C	p.Glu1630Ala	missense_variant	Exon 10 of 23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3	c.4811A>C	p.Glu1604Ala	missense_variant	Exon 9 of 22	5	NM_001371242.2	ENSP00000488010.2

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

GnomAD2 exomes AF: 0.931 AC: 233875 AN: 251108 AF XY: 0.933

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 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

African (AFR) AF: 0.937 AC: 31305 AN: 33426

American (AMR) AF: 0.921 AC: 41176 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 23825 AN: 26118

East Asian (EAS) AF: 0.934 AC: 37029 AN: 39662

South Asian (SAS) AF: 0.960 AC: 82775 AN: 86236

European-Finnish (FIN) AF: 0.932 AC: 49775 AN: 53408

Middle Eastern (MID) AF: 0.880 AC: 5074 AN: 5766

European-Non Finnish (NFE) AF: 0.928 AC: 1031891 AN: 1111648

Other (OTH) AF: 0.926 AC: 55927 AN: 60386

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

African (AFR) AF: 0.938 AC: 38971 AN: 41530

American (AMR) AF: 0.919 AC: 14056 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3470

East Asian (EAS) AF: 0.938 AC: 4863 AN: 5184

South Asian (SAS) AF: 0.965 AC: 4654 AN: 4824

European-Finnish (FIN) AF: 0.921 AC: 9769 AN: 10610

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63124 AN: 68018

Other (OTH) AF: 0.916 AC: 1937 AN: 2114

Alfa AF: 0.928 Hom.: 295059

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
DEOGEN2	Benign	0.061	.;T
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
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Benign	0.18
Sift	Benign	0.43	.;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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs783396; hg19: chr6-106987370; COSMIC: COSV108211742; COSMIC: COSV108211742;