chr16-21261270-G-C

Position:

chr16-21261270-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001376256.1(CRYM):c.864C>G(p.Thr288=) 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

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 -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 id is 44241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21261270-G-C is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYM	NM_001376256.1 linkuse as main transcript	c.864C>G	p.Thr288=	synonymous_variant	7/8	ENST00000572914.2
CRYM	NM_001888.5 linkuse as main transcript	c.864C>G	p.Thr288=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYM	ENST00000572914.2 linkuse as main transcript	c.864C>G	p.Thr288=	synonymous_variant	7/8	2	NM_001376256.1	P1

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

GnomAD3 exomes

AF:

0.442

AC:

111014

AN:

251314

Hom.:

25858

AF XY:

0.439

AC XY:

59594

AN XY:

135846

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 SAS exome

AF:

0.462

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

Gnomad4 AFR exome

AF:

0.785

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.522

AC:

79193

AN:

151818

Hom.:

22588

Cov.:

AF XY:

0.523

AC XY:

38791

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.771

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.417

Gnomad4 OTH

AF:

0.472

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

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Thr288Thr in Exon 09 of CRYM: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 41.4% (2906/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs14122). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal dominant nonsyndromic hearing loss 40

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.018

DANN

Benign

0.72

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

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