6-106512814-C-G

Variant names:

• chr6-106512814-C-G
• rs373973928
• NM_001371242.2:c.1697C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371242.2(CRYBG1):​c.1697C>G​(p.Ala566Gly) 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. 15/21 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. A566V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06485322).

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.1697C>G	p.Ala566Gly	missense	Exon 3 of 22	NP_001358171.1	Q9Y4K1-3
	CRYBG1	NM_001624.4		c.473C>G	p.Ala158Gly	missense	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.1697C>G	p.Ala566Gly	missense	Exon 3 of 22	ENSP00000488010.2	Q9Y4K1-3
	CRYBG1	ENST00000651520.1		c.1538C>G	p.Ala513Gly	missense	Exon 2 of 2	ENSP00000499126.1	A0A494C1M5
	ENSG00000300544	ENST00000772631.1		n.164G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.20
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.24		Gain of loop (P = 0.0079)
MVP		0.44
MPC		0.086
ClinPred		0.086	T
GERP RS		1.2
Varity_R		0.064
gMVP		0.19
Mutation Taster		=99/1	polymorphism

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: rs373973928; hg19: chr6-106960689;