chr16-21261044-T-C

Position:

• chr16-21261044-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001376256.1(CRYM):​c.880+210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 618,710 control chromosomes in the GnomAD database, including 19,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5284 hom., cov: 32)
  • Exomes 𝑓: 0.23 (13812 hom.)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0260

Genes affected

CRYM (HGNC:2418): (crystallin mu) Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 16-21261044-T-C is Benign according to our data. Variant chr16-21261044-T-C is described in ClinVar as [Benign]. Clinvar id is 1274122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1	c.880+210A>G		intron_variant		ENST00000572914.2
CRYM	NM_001888.5	c.880+210A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2	c.880+210A>G		intron_variant		2	NM_001376256.1	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38936 AN: 151954 Hom.: 5285 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.231 AC: 107748 AN: 466638 Hom.: 13812 Cov.: 3 AF XY: 0.232 AC XY: 57710 AN XY: 248342

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.00170

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.256 AC: 38948 AN: 152072 Hom.: 5284 Cov.: 32 AF XY: 0.256 AC XY: 19035 AN XY: 74310

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.200

Alfa AF: 0.248 Hom.: 2259

Bravo AF: 0.248

Asia WGS AF: 0.118 AC: 414 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.0
DANN	Benign	0.52

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: rs7194883; hg19: chr16-21272365;