NM_001371242.2:c.4811A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371242.2(CRYBG1):​c.4811A>G​(p.Glu1604Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 31)
• 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: 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=0.13702169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.4811A>G	p.Glu1604Gly	missense_variant	Exon 9 of 22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.3587A>G	p.Glu1196Gly	missense_variant	Exon 7 of 20		NP_001615.2
CRYBG1	XM_047418270.1	c.4889A>G	p.Glu1630Gly	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>G	p.Glu1604Gly	missense_variant	Exon 9 of 22	5	NM_001371242.2	ENSP00000488010.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	.;D
REVEL	Benign	0.19
Sift	Benign	0.051	.;T
Sift4G	Uncertain	0.010	D;D
Polyphen		0.013	.;B
Vest4		0.26
MutPred		0.45		.;Gain of catalytic residue at A1197 (P = 0.0606);
MVP		0.52
MPC		0.20
ClinPred		0.39	T
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.58
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;