1-26322170-C-G

Variant names:

• chr1-26322170-C-G
• rs776308885
• NM_001039775.4:c.4891G>C

Variant summary

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

The NM_001039775.4(CRYBG2):​c.4891G>C​(p.Val1631Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V1631M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRYBG2 NM_001039775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

Genes affected

CRYBG2 (HGNC:17295): (crystallin beta-gamma domain containing 2) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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_001039775.4. 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
	CRYBG2	NM_001039775.4	MANE Select	c.4891G>C	p.Val1631Leu	missense	Exon 19 of 20	NP_001034864.2	Q8N1P7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG2	ENST00000308182.10	TSL:5 MANE Select	c.4891G>C	p.Val1631Leu	missense	Exon 19 of 20	ENSP00000310435.6	Q8N1P7
	CRYBG2	ENST00000475866.3	TSL:4	c.5863G>C	p.Val1955Leu	missense	Exon 21 of 22	ENSP00000428746.2	E7ET48
	CRYBG2	ENST00000374208.1	TSL:5	n.369G>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251172 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.45	T
PhyloP100		1.7
PrimateAI	Uncertain	0.57	T
REVEL	Uncertain	0.31
Sift4G	Uncertain	0.015	D
Vest4		0.66
MVP		0.71
ClinPred		0.89	D
GERP RS		5.1
gMVP		0.60
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs776308885; hg19: chr1-26648661;