chr11-111908788-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001289808.2(CRYAB):ā€‹c.504T>Cā€‹(p.Ala168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

CRYAB
NM_001289808.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.42
Variant links:
Genes affected
CRYAB (HGNC:2389): (crystallin alpha B) Mammalian lens crystallins are divided into alpha, beta, and gamma families. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 11-111908788-A-G is Benign according to our data. Variant chr11-111908788-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1101698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.41 with no splicing effect.
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRYABNM_001289808.2 linkuse as main transcriptc.504T>C p.Ala168= synonymous_variant 3/3 ENST00000650687.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRYABENST00000650687.2 linkuse as main transcriptc.504T>C p.Ala168= synonymous_variant 3/3 NM_001289808.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251456
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460762
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726704
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1II Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 19, 2022- -
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 19, 2019This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
9.0
DANN
Benign
0.74

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.

Other links and lift over

dbSNP: rs782361571; hg19: chr11-111779512; API