16-21260990-G-A

Position:

• chr16-21260990-G-A

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+264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 546,070 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (93 hom., cov: 32)
  • Exomes 𝑓: 0.017 (306 hom.)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650

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=-0.7).
• BP6: Variant 16-21260990-G-A is Benign according to our data. Variant chr16-21260990-G-A is described in ClinVar as [Benign]. Clinvar id is 1178401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1	c.880+264C>T		intron_variant		ENST00000572914.2
CRYM	NM_001888.5	c.880+264C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2	c.880+264C>T		intron_variant		2	NM_001376256.1	P1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2547 AN: 152184 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0171 AC: 6728 AN: 393768 Hom.: 306 AF XY: 0.0164 AC XY: 3441 AN XY: 209464

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.0782

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0174

Gnomad4 FIN exome AF: 0.0463

Gnomad4 NFE exome AF: 0.00158

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0167 AC: 2549 AN: 152302 Hom.: 93 Cov.: 32 AF XY: 0.0218 AC XY: 1623 AN XY: 74462

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0684

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00336 Hom.: 0

Bravo AF: 0.0157

Asia WGS AF: 0.0850 AC: 297 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	clinical testing	GeneDx	Dec 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.1
DANN	Benign	0.64

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: rs77562083; hg19: chr16-21272311;