1-26322048-C-T

Variant names:

• chr1-26322048-C-T
• NM_001039775.4:c.4906G>A

Variant summary

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

The NM_001039775.4(CRYBG2):​c.4906G>A​(p.Gly1636Ser) 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. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRYBG2 NM_001039775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.456
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14386058).

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.4906G>A	p.Gly1636Ser	missense	Exon 20 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.4906G>A	p.Gly1636Ser	missense	Exon 20 of 20	ENSP00000310435.6	Q8N1P7
	CRYBG2	ENST00000475866.3	TSL:4	c.5878G>A	p.Gly1960Ser	missense	Exon 22 of 22	ENSP00000428746.2	E7ET48
	CRYBG2	ENST00000374208.1	TSL:5	n.384G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454324 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721686

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39442

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105896

Other (OTH) AF: 0.00 AC: 0 AN: 59964

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.82
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.46
PrimateAI	Benign	0.41	T
REVEL	Benign	0.050
Sift4G	Benign	0.66	T
Vest4		0.15
MVP		0.25
ClinPred		0.71	D
GERP RS		3.4
gMVP		0.29
Mutation Taster		=87/13	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

hg19: chr1-26648539;