3-186542170-C-T

Position:

• chr3-186542170-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307944.6(CRYGS):​c.21+2136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,214 control chromosomes in the GnomAD database, including 1,754 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1754 hom., cov: 32)
• Consequence: CRYGS ENST00000307944.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

Genes affected

CRYGS (HGNC:2417): (crystallin gamma S) Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. This gene encodes a protein initially considered to be a beta-crystallin but the encoded protein is monomeric and has greater sequence similarity to other gamma-crystallins. This gene encodes the most significant gamma-crystallin in adult eye lens tissue. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGS	NM_017541.4	c.21+2136G>A		intron_variant		ENST00000307944.6	NP_060011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGS	ENST00000307944.6	c.21+2136G>A		intron_variant		1	NM_017541.4	ENSP00000312099	P1
CRYGS	ENST00000392499.6	c.21+2136G>A		intron_variant		2		ENSP00000376287	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21176 AN: 152096 Hom.: 1753 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21189 AN: 152214 Hom.: 1754 Cov.: 32 AF XY: 0.145 AC XY: 10764 AN XY: 74424

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0634 Hom.: 87

Bravo AF: 0.140

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs3774803; hg19: chr3-186259959;