1-26322039-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001039775.4(CRYBG2):c.4915C>T(p.Arg1639Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,606,728 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

CRYBG2
NM_001039775.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.51

Variant links:

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]

CRYBG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016377538).

BP6

Variant 1-26322039-G-A is Benign according to our data. Variant chr1-26322039-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3077868.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG2	NM_001039775.4 link	c.4915C>T	p.Arg1639Trp	missense_variant	Exon 20 of 20	ENST00000308182.10	NP_001034864.2	Q8N1P7Q9NWG5
CRYBG2	XM_011541673.3 link	c.5086C>T	p.Arg1696Trp	missense_variant	Exon 20 of 20		XP_011539975.1
CRYBG2	XM_005245918.3 link	c.4915C>T	p.Arg1639Trp	missense_variant	Exon 20 of 20		XP_005245975.1	Q8N1P7
CRYBG2	XM_011541672.2 link	c.4879C>T	p.Arg1627Trp	missense_variant	Exon 19 of 19		XP_011539974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRYBG2	ENST00000308182.10 link	c.4915C>T	p.Arg1639Trp	missense_variant	Exon 20 of 20	5	NM_001039775.4	ENSP00000310435.6	Q8N1P7
CRYBG2	ENST00000475866.3 link	c.5887C>T	p.Arg1963Trp	missense_variant	Exon 22 of 22	4		ENSP00000428746.2	E7ET48
CRYBG2	ENST00000374208.1 link	n.393C>T		non_coding_transcript_exon_variant	Exon 4 of 4	5
CRYBG2	ENST00000374211.5 link	n.529C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000988

AC:

247

AN:

250018

Hom.:

AF XY:

0.00104

AC XY:

140

AN XY:

135054

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00206

AC:

2996

AN:

1454502

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1424

AN XY:

721804

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152226

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00161

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.000816

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00154

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4915C>T (p.R1639W) alteration is located in exon 20 (coding exon 19) of the AIM1L gene. This alteration results from a C to T substitution at nucleotide position 4915, causing the arginine (R) at amino acid position 1639 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CRYBG2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.33

REVEL

Benign

0.18

Sift4G

Uncertain

0.0020

.;D

Vest4

0.54

MVP

0.56

ClinPred

0.058

GERP RS

3.2

gMVP

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over