rs226045

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001376256.1(CRYM):c.325-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,609,228 control chromosomes in the GnomAD database, including 52,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5930 hom., cov: 32)

Exomes 𝑓: 0.24 ( 46264 hom. )

Consequence

CRYM
NM_001376256.1 intron

Scores

Splicing: ADA: 0.0001049

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.00100

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 16-21275606-A-G is Benign according to our data. Variant chr16-21275606-A-G is described in ClinVar as [Benign]. Clinvar id is 44237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21275606-A-G is described in Lovd as [Benign].

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 rank	MANE	Protein	UniProt
CRYM	NM_001376256.1 link	c.325-12T>C		intron_variant	Intron 2 of 7	ENST00000572914.2	NP_001363185.1
CRYM	NM_001888.5 link	c.325-12T>C		intron_variant	Intron 4 of 9		NP_001879.1	Q14894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYM	ENST00000572914.2 link	c.325-12T>C		intron_variant	Intron 2 of 7	2	NM_001376256.1	ENSP00000461904.2		Q14894I3NI53

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40801

AN:

151968

Hom.:

5924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.225

AC:

56578

AN:

250966

Hom.:

7400

AF XY:

0.226

AC XY:

30606

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.244

AC:

355862

AN:

1457142

Hom.:

46264

Cov.:

AF XY:

0.243

AC XY:

176043

AN XY:

725170

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.00113

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.268

AC:

40833

AN:

152086

Hom.:

5930

Cov.:

AF XY:

0.266

AC XY:

19786

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.362

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.251

Hom.:

914

Bravo

AF:

0.264

Asia WGS

AF:

0.0970

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

325-12T>C in Intron 04 of CRYM: This variant is not expected to have clinical si gnificance because it has been identified in 36.1% (1351/3738) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs226045). -

Autosomal dominant nonsyndromic hearing loss 40

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over