6-106571760-A-G

Position:

• chr6-106571760-A-G

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.*3194A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 451,632 control chromosomes in the GnomAD database, including 3,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1756 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1756 hom.)
• Consequence: CRYBG1 NM_001371242.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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=-0.94).
• BP6: Variant 6-106571760-A-G is Benign according to our data. Variant chr6-106571760-A-G is described in ClinVar as [Benign]. Clinvar id is 1228467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG1	NM_001371242.2	c.*3194A>G		3_prime_UTR_variant	22/22	ENST00000633556.3
RTN4IP1	NM_032730.5	c.*236T>C		3_prime_UTR_variant	9/9	ENST00000369063.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4IP1	ENST00000369063.8	c.*236T>C		3_prime_UTR_variant	9/9	1	NM_032730.5	P1
CRYBG1	ENST00000633556.3	c.*3194A>G		3_prime_UTR_variant	22/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21595 AN: 152132 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.0999 AC: 29918 AN: 299382 Hom.: 1756 Cov.: 0 AF XY: 0.101 AC XY: 16093 AN XY: 158888

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.142 AC: 21597 AN: 152250 Hom.: 1756 Cov.: 32 AF XY: 0.142 AC XY: 10541 AN XY: 74446

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.155

Alfa AF: 0.123 Hom.: 1163

Bravo AF: 0.145

Asia WGS AF: 0.152 AC: 532 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9320183; hg19: chr6-107019635;