dbSNP rs73906469: CRYAA:c.189+71G>A (chr21-43169359-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000394.4(CRYAA):c.189+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000059 ( 0 hom., cov: 14)

Exomes 𝑓: 0.000020 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CRYAA
NM_000394.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.493

Variant links:

Genes affected

CRYAA (HGNC:2388): (crystallin alpha A) 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. Post-translational modifications decrease the ability to chaperone. 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. Defects in this gene cause autosomal dominant congenital cataract (ADCC). [provided by RefSeq, Jan 2014]

CRYAA links:

LOC107987300 (HGNC:):

LOC107987300 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYAA	NM_000394.4 link	c.189+71G>A		intron_variant	Intron 1 of 2	ENST00000291554.6	NP_000385.1	P02489
LOC107987300	XR_007067885.1 link	n.546+1678C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRYAA	ENST00000291554.6 link	c.189+71G>A	intron_variant	Intron 1 of 2	1	NM_000394.4	ENSP00000291554.2	P02489
CRYAA	ENST00000482775.1 link	n.202+71G>A	intron_variant	Intron 1 of 3	5
CRYAA	ENST00000398133.5 link	c.-366G>A	upstream_gene_variant		3		ENSP00000381201.1	E7EWH7

Frequencies

GnomAD3 genomes

AF:

0.0000589

AC:

AN:

101838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000221

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000227

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000202

AC:

AN:

395392

Hom.:

Cov.:

AF XY:

0.0000190

AC XY:

AN XY:

210378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11200

American (AMR)

AF:

0.00

AC:

AN:

23958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12238

East Asian (EAS)

AF:

0.0000321

AC:

AN:

31132

South Asian (SAS)

AF:

0.0000412

AC:

AN:

48596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1678

European-Non Finnish (NFE)

AF:

0.0000182

AC:

AN:

220270

Other (OTH)

AF:

0.0000450

AC:

AN:

22202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000589

AC:

AN:

101916

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

49340

show subpopulations

African (AFR)

AF:

0.000143

AC:

AN:

27940

American (AMR)

AF:

0.00

AC:

AN:

10654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2416

East Asian (EAS)

AF:

0.000222

AC:

AN:

4508

South Asian (SAS)

AF:

0.00

AC:

AN:

3358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.0000227

AC:

AN:

44130

Other (OTH)

AF:

0.00

AC:

AN:

1320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.82

(source)

DANN

Benign

0.70

PhyloP100

-0.49

PromoterAI

0.00010

Neutral

(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.

rs73906469

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over