16-21258960-A-C

Position:

• chr16-21258960-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001376256.1(CRYM):​c.881-115T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 809,204 control chromosomes in the GnomAD database, including 605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (408 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (197 hom.)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-21258960-A-C is Benign according to our data. Variant chr16-21258960-A-C is described in ClinVar as [Benign]. Clinvar id is 1283744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1	c.881-115T>G		intron_variant		ENST00000572914.2
CRYM	NM_001888.5	c.881-115T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2	c.881-115T>G		intron_variant		2	NM_001376256.1	P1

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6083 AN: 152156 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.00557 AC: 3658 AN: 656930 Hom.: 197 AF XY: 0.00455 AC XY: 1611 AN XY: 354366

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.00775

Gnomad4 ASJ exome AF: 0.00101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000426

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000637

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0401 AC: 6109 AN: 152274 Hom.: 408 Cov.: 32 AF XY: 0.0391 AC XY: 2910 AN XY: 74458

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0313 Hom.: 29

Bravo AF: 0.0457

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs76286936; hg19: chr16-21270281;