rs14122

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001376256.1(CRYM):c.864C>G(p.Thr288Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,611,502 control chromosomes in the GnomAD database, including 159,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22588 hom., cov: 30)

Exomes 𝑓: 0.43 ( 137011 hom. )

Consequence

CRYM
NM_001376256.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.33

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 40
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CRYM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-21261270-G-C is Benign according to our data. Variant chr16-21261270-G-C is described in ClinVar as Benign. ClinVar VariationId is 44241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376256.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYM	NM_001376256.1	MANE Select	c.864C>G	p.Thr288Thr	synonymous	Exon 7 of 8	NP_001363185.1	Q14894
	CRYM	NM_001888.5		c.864C>G	p.Thr288Thr	synonymous	Exon 9 of 10	NP_001879.1	Q14894

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRYM	ENST00000572914.2	TSL:2 MANE Select	c.864C>G	p.Thr288Thr	synonymous	Exon 7 of 8	ENSP00000461904.2	Q14894
CRYM	ENST00000219599.8	TSL:1	c.864C>G	p.Thr288Thr	synonymous	Exon 9 of 10	ENSP00000219599.3	Q14894
CRYM	ENST00000574448.5	TSL:1	n.*504C>G		non_coding_transcript_exon	Exon 8 of 10	ENSP00000459982.1	I3L2W5

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79109

AN:

151700

Hom.:

22560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.771

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.473

GnomAD2 exomes

AF:

0.442

AC:

111014

AN:

251314

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.784

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.471

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.428

AC:

624510

AN:

1459684

Hom.:

137011

Cov.:

AF XY:

0.428

AC XY:

310619

AN XY:

726316

show subpopulations

African (AFR)

AF:

0.785

AC:

26251

AN:

33444

American (AMR)

AF:

0.381

AC:

17027

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

12384

AN:

26112

East Asian (EAS)

AF:

0.358

AC:

14196

AN:

39688

South Asian (SAS)

AF:

0.460

AC:

39665

AN:

86204

European-Finnish (FIN)

AF:

0.474

AC:

25309

AN:

53412

Middle Eastern (MID)

AF:

0.472

AC:

2701

AN:

5722

European-Non Finnish (NFE)

AF:

0.415

AC:

460361

AN:

1110060

Other (OTH)

AF:

0.441

AC:

26616

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

18004

36009

54013

72018

90022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14222

28444

42666

56888

71110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.522

AC:

79193

AN:

151818

Hom.:

22588

Cov.:

AF XY:

0.523

AC XY:

38791

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.771

AC:

31899

AN:

41380

American (AMR)

AF:

0.458

AC:

6987

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1600

AN:

3468

East Asian (EAS)

AF:

0.306

AC:

1575

AN:

5144

South Asian (SAS)

AF:

0.445

AC:

2139

AN:

4812

European-Finnish (FIN)

AF:

0.491

AC:

5160

AN:

10518

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28325

AN:

67926

Other (OTH)

AF:

0.472

AC:

993

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1678

3356

5033

6711

8389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

3602

Bravo

AF:

0.524

Asia WGS

AF:

0.447

AC:

1556

AN:

3478

EpiCase

AF:

0.422

EpiControl

AF:

0.412

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Autosomal dominant nonsyndromic hearing loss 40 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.018

(source)

DANN

Benign

0.72

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over