16-21290151-T-C

Variant names:

• chr16-21290151-T-C
• rs226047
• ENST00000219599.8:c.-192-11191A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

CRYM Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 40

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000299922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CRYM	NM_001888.5	c.-192-11191A>G		intron_variant	Intron 1 of 9		NP_001879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYM	ENST00000219599.8	c.-192-11191A>G		intron_variant	Intron 1 of 9	1		ENSP00000219599.3
ENSG00000299922	ENST00000767446.1	n.6T>C		non_coding_transcript_exon_variant	Exon 1 of 4
ENSG00000299922	ENST00000767447.1	n.6T>C		non_coding_transcript_exon_variant	Exon 1 of 3

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

African (AFR) AF: 0.346 AC: 14324 AN: 41456

American (AMR) AF: 0.271 AC: 4142 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1008 AN: 5136

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4800

European-Finnish (FIN) AF: 0.353 AC: 3723 AN: 10554

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16680 AN: 67946

Other (OTH) AF: 0.222 AC: 467 AN: 2106

Alfa AF: 0.245 Hom.: 12531

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs226047; hg19: chr16-21301472;