Genetic Variant NM_001371242.2:c.*2846C>T (chr6-106571412-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001371242.2(CRYBG1):c.*2846C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,378 control chromosomes in the GnomAD database, including 2,477 homozygotes. 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 0.16 ( 2476 hom., cov: 32)

Exomes 𝑓: 0.11 ( 1 hom. )

Consequence

CRYBG1
NM_001371242.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Publications

6 publications found

Variant links:

Genes affected

CRYBG1 (HGNC:356): (crystallin beta-gamma domain containing 1) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG1 links:

RTN4IP1 (HGNC:18647): (reticulon 4 interacting protein 1) This gene encodes a mitochondrial protein that interacts with reticulon 4, which is a potent inhibitor of regeneration following spinal cord injury. This interaction may be important for reticulon-induced inhibition of neurite growth. Mutations in this gene can cause optic atrophy 10, with or without ataxia, cognitive disability, and seizures. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

RTN4IP1 Gene-Disease associations (from GenCC):

optic atrophy 10 with or without ataxia, intellectual disability, and seizures
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
autosomal recessive optic atrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RTN4IP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG1	NM_001371242.2 link	c.*2846C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000633556.3	NP_001358171.1
RTN4IP1	NM_032730.5 link	c.*584G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000369063.8	NP_116119.2	Q8WWV3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3 link	c.*2846C>T		3_prime_UTR_variant	Exon 22 of 22	5	NM_001371242.2	ENSP00000488010.2		A0A0J9YWL0
RTN4IP1	ENST00000369063.8 link	c.*584G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_032730.5	ENSP00000358059.3		Q8WWV3-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24744

AN:

151988

Hom.:

2474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.164

GnomAD4 exome

AF:

0.107

AC:

AN:

272

Hom.:

Cov.:

AF XY:

0.109

AC XY:

AN XY:

156

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.111

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0957

AC:

AN:

230

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.163

AC:

24751

AN:

152106

Hom.:

2476

Cov.:

AF XY:

0.162

AC XY:

12022

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.282

AC:

11669

AN:

41450

American (AMR)

AF:

0.131

AC:

2011

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

439

AN:

3470

East Asian (EAS)

AF:

0.142

AC:

735

AN:

5176

South Asian (SAS)

AF:

0.133

AC:

640

AN:

4820

European-Finnish (FIN)

AF:

0.123

AC:

1305

AN:

10586

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.110

AC:

7474

AN:

67986

Other (OTH)

AF:

0.163

AC:

345

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1035

2069

3104

4138

5173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.133

Hom.:

4232

Bravo

AF:

0.169

Asia WGS

AF:

0.155

AC:

542

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

(source)

DANN

Benign

0.47

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over