Variant chr2-208128371-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020989.4(CRYGC):c.357C>T(p.Ser119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,614,150 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 34 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 49 hom. )

Consequence

CRYGC
NM_020989.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

CRYGC (HGNC:2410): (crystallin gamma C) This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]

CRYGC links:

LOC100507443 (HGNC:):

LOC100507443 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-208128371-G-A is Benign according to our data. Variant chr2-208128371-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-208128371-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1914/152258) while in subpopulation AFR AF= 0.0431 (1792/41538). AF 95% confidence interval is 0.0415. There are 34 homozygotes in gnomad4. There are 935 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1914 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYGC	NM_020989.4 linkuse as main transcript	c.357C>T	p.Ser119=	synonymous_variant	3/3	ENST00000282141.4
LOC100507443	NR_038437.1 linkuse as main transcript	n.98-8685G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYGC	ENST00000282141.4 linkuse as main transcript	c.357C>T	p.Ser119=	synonymous_variant	3/3	1	NM_020989.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1901

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00340

AC:

854

AN:

251428

Hom.:

AF XY:

0.00249

AC XY:

338

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0451

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00136

AC:

1990

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

874

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0451

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.0126

AC:

1914

AN:

152258

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

935

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 06, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nuclear pulverulent cataract

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.7

DANN

Benign

0.78

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

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