rs9320182

Positions:

• chr6-106571412-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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 -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/exons	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.*2846C>T		3_prime_UTR_variant	22/22	ENST00000633556.3	NP_001358171.1
RTN4IP1	NM_032730.5	c.*584G>A		3_prime_UTR_variant	9/9	ENST00000369063.8	NP_116119.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4IP1	ENST00000369063.8	c.*584G>A		3_prime_UTR_variant	9/9	1	NM_032730.5	ENSP00000358059	P1
CRYBG1	ENST00000633556.3	c.*2846C>T		3_prime_UTR_variant	22/22	5	NM_001371242.2	ENSP00000488010	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24744 AN: 151988 Hom.: 2474 Cov.: 32

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: 29 AN: 272 Hom.: 1 Cov.: 0 AF XY: 0.109 AC XY: 17 AN XY: 156

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.111

Gnomad4 EAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.163 AC: 24751 AN: 152106 Hom.: 2476 Cov.: 32 AF XY: 0.162 AC XY: 12022 AN XY: 74380

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.163

Alfa AF: 0.123 Hom.: 2100

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
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9320182; hg19: chr6-107019287;