rs61736036

Variant names:

• chr2-208128371-G-A
• rs61736036
• NM_020989.4:c.357C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020989.4(CRYGC):​c.357C>T​(p.Ser119Ser) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.51

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]

LOC100507443 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1914 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYGC	NM_020989.4	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 3 of 3	ENST00000282141.4	NP_066269.1
LOC100507443	NR_038437.1	n.98-8685G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGC	ENST00000282141.4	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 3 of 3	1	NM_020989.4	ENSP00000282141.3

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1901 AN: 152140 Hom.: 33 Cov.: 33

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

GnomAD2 exomes AF: 0.00340 AC: 854 AN: 251428 AF XY: 0.00249

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 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.: 49 Cov.: 31 AF XY: 0.00120 AC XY: 874 AN XY: 727248

Gnomad4 AFR exome AF: 0.0451 AC: 1510 AN: 33480

Gnomad4 AMR exome AF: 0.00239 AC: 107 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000139 AC: 12 AN: 86258

Gnomad4 FIN exome AF: 0.000243 AC: 13 AN: 53418

Gnomad4 NFE exome AF: 0.0000980 AC: 109 AN: 1112012

Gnomad4 Remaining exome AF: 0.00358 AC: 216 AN: 60396

GnomAD4 genome AF: 0.0126 AC: 1914 AN: 152258 Hom.: 34 Cov.: 33 AF XY: 0.0126 AC XY: 935 AN XY: 74434

Gnomad4 AFR AF: 0.0431 AC: 0.0431412 AN: 0.0431412

Gnomad4 AMR AF: 0.00471 AC: 0.00470773 AN: 0.00470773

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000622407 AN: 0.000622407

Gnomad4 FIN AF: 0.000283 AC: 0.000282699 AN: 0.000282699

Gnomad4 NFE AF: 0.000265 AC: 0.000264597 AN: 0.000264597

Gnomad4 OTH AF: 0.0104 AC: 0.010397 AN: 0.010397

Alfa AF: 0.00664 Hom.: 9

Bravo AF: 0.0142

Asia WGS AF: 0.00462 AC: 16 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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 06, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nuclear pulverulent cataract Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.7
DANN	Benign	0.78
Mutation Taster		=99/1	polymorphism

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: rs61736036; hg19: chr2-208993095;