6-106571786-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001371242.2(CRYBG1):c.*3220T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 481,260 control chromosomes in the GnomAD database, including 4,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2438 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2257 hom.)
• Consequence: CRYBG1 NM_001371242.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-106571786-T-C is Benign according to our data. Variant chr6-106571786-T-C is described in ClinVar as [Benign]. Clinvar id is 1238463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG1	NM_001371242.2	c.*3220T>C		3_prime_UTR_variant	22/22	ENST00000633556.3
RTN4IP1	NM_032730.5	c.*210A>G		3_prime_UTR_variant	9/9	ENST00000369063.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4IP1	ENST00000369063.8	c.*210A>G		3_prime_UTR_variant	9/9	1	NM_032730.5	P1
CRYBG1	ENST00000633556.3	c.*3220T>C		3_prime_UTR_variant	22/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24717 AN: 151962 Hom.: 2436 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.108 AC: 35625 AN: 329180 Hom.: 2257 Cov.: 3 AF XY: 0.109 AC XY: 18901 AN XY: 174190

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0959

Gnomad4 NFE exome AF: 0.0964

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.163 AC: 24724 AN: 152080 Hom.: 2438 Cov.: 33 AF XY: 0.161 AC XY: 11987 AN XY: 74330

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.164

Alfa AF: 0.126 Hom.: 538

Bravo AF: 0.169

Asia WGS AF: 0.155 AC: 542 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.1
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9486408; hg19: chr6-107019661;