1-26321976-C-G

Variant names:

• chr1-26321976-C-G
• NM_001039775.4:c.4978G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039775.4(CRYBG2):​c.4978G>C​(p.Val1660Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 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. V1660M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CRYBG2 NM_001039775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32961762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG2	NM_001039775.4	c.4978G>C	p.Val1660Leu	missense_variant	Exon 20 of 20	ENST00000308182.10	NP_001034864.2
CRYBG2	XM_011541673.3	c.5149G>C	p.Val1717Leu	missense_variant	Exon 20 of 20		XP_011539975.1
CRYBG2	XM_005245918.3	c.4978G>C	p.Val1660Leu	missense_variant	Exon 20 of 20		XP_005245975.1
CRYBG2	XM_011541672.2	c.4942G>C	p.Val1648Leu	missense_variant	Exon 19 of 19		XP_011539974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG2	ENST00000308182.10	c.4978G>C	p.Val1660Leu	missense_variant	Exon 20 of 20	5	NM_001039775.4	ENSP00000310435.6
CRYBG2	ENST00000475866.3	c.5950G>C	p.Val1984Leu	missense_variant	Exon 22 of 22	4		ENSP00000428746.2
CRYBG2	ENST00000374208.1	n.456G>C		non_coding_transcript_exon_variant	Exon 4 of 4	5
CRYBG2	ENST00000374211.5	n.592G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1429724 Hom.: 0 Cov.: 29 AF XY: 0.00000142 AC XY: 1 AN XY: 705476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.97
Eigen	Benign	0.027
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Uncertain	-0.25	T
PrimateAI	Uncertain	0.63	T
REVEL	Uncertain	0.30
Sift4G	Benign	0.23	.;T
Vest4		0.25
MVP		0.72
ClinPred		0.74	D
GERP RS		5.3
gMVP		0.21

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26648467;