16-21261216-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001376256.1(CRYM):c.880+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,505,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.645

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-21261216-G-A is Benign according to our data. Variant chr16-21261216-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1318953.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1	c.880+38C>T		intron_variant		ENST00000572914.2
CRYM	NM_001888.5	c.880+38C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2	c.880+38C>T		intron_variant		2	NM_001376256.1	P1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000498 AC: 125 AN: 251102 Hom.: 0 AF XY: 0.000545 AC XY: 74 AN XY: 135728

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00425

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000239 AC: 323 AN: 1353294 Hom.: 1 Cov.: 21 AF XY: 0.000243 AC XY: 165 AN XY: 679864

Gnomad4 AFR exome AF: 0.0000974

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000787

Gnomad4 EAS exome AF: 0.00158

Gnomad4 SAS exome AF: 0.000274

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000177

Gnomad4 OTH exome AF: 0.000617

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74478

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000261

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.1
Dann	Benign	0.74

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: rs149727600; hg19: chr16-21272537;