16-21290151-T-C

Position:

• chr16-21290151-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000219599.8(CRYM):​c.-192-11191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,938 control chromosomes in the GnomAD database, including 6,113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6113 hom., cov: 30)
• Consequence: CRYM ENST00000219599.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001888.5	c.-192-11191A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000219599.8	c.-192-11191A>G		intron_variant		1		P1
CRYM	ENST00000576703.5	c.-44-11982A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42192 AN: 151820 Hom.: 6104 Cov.: 30

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42236 AN: 151938 Hom.: 6113 Cov.: 30 AF XY: 0.282 AC XY: 20967 AN XY: 74266

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.222

Alfa AF: 0.231 Hom.: 6709

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs226047; hg19: chr16-21301472;