6-106512924-C-T

Variant names:

• chr6-106512924-C-T
• rs746845033
• NM_001371242.2:c.1807C>T

Variant summary

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

The NM_001371242.2(CRYBG1):​c.1807C>T​(p.Arg603*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRYBG1 NM_001371242.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 1 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]

ENSG00000300544 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1807C>T	p.Arg603*	stop_gained	Exon 3 of 22	NP_001358171.1	Q9Y4K1-3
	CRYBG1	NM_001624.4		c.583C>T	p.Arg195*	stop_gained	Exon 1 of 20	NP_001615.2	Q9Y4K1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG1	ENST00000633556.3	TSL:5 MANE Select	c.1807C>T	p.Arg603*	stop_gained	Exon 3 of 22	ENSP00000488010.2	Q9Y4K1-3
	CRYBG1	ENST00000651520.1		c.1648C>T	p.Arg550*	stop_gained	Exon 2 of 2	ENSP00000499126.1	A0A494C1M5
	ENSG00000300544	ENST00000772631.1		n.54G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.24	N
PhyloP100		1.5
Vest4		0.87
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=2/198	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs746845033; hg19: chr6-106960799;