NM_001371242.2:c.4811A>T

Variant names:

• chr6-106539495-A-T
• rs783396
• NM_001371242.2:c.4811A>T

Variant summary

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

The NM_001371242.2(CRYBG1):​c.4811A>T​(p.Glu1604Val) 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. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 44 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]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.4811A>T	p.Glu1604Val	missense_variant	Exon 9 of 22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.3587A>T	p.Glu1196Val	missense_variant	Exon 7 of 20		NP_001615.2
CRYBG1	XM_047418270.1	c.4889A>T	p.Glu1630Val	missense_variant	Exon 10 of 23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3	c.4811A>T	p.Glu1604Val	missense_variant	Exon 9 of 22	5	NM_001371242.2	ENSP00000488010.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461496 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.95	T
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.3	.;D
REVEL	Benign	0.29
Sift	Uncertain	0.028	.;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.0020	.;B
Vest4		0.26
MutPred		0.60		.;Gain of sheet (P = 0.0344);
MVP		0.57
MPC		0.10
ClinPred		0.31	T
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.70
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.23		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs783396; hg19: chr6-106987370;