rs226038

Positions:

• chr16-21277017-C-A
• chr16-21277017-C-T

Variant summary

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

The NM_001376256.1(CRYM):​c.324+414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,994 control chromosomes in the GnomAD database, including 5,926 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 0.27 (5926 hom., cov: 32)
• Consequence: CRYM NM_001376256.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1	c.324+414G>T		intron_variant		ENST00000572914.2
CRYM	NM_001888.5	c.324+414G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2	c.324+414G>T		intron_variant		2	NM_001376256.1	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40768 AN: 151874 Hom.: 5920 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.268 AC: 40800 AN: 151994 Hom.: 5926 Cov.: 32 AF XY: 0.266 AC XY: 19772 AN XY: 74280

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.208

Alfa AF: 0.178 Hom.: 444

Bravo AF: 0.264

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs226038; hg19: chr16-21288338;