NM_001371242.2:c.*3225A>C

Variant names:

• chr6-106571791-A-C
• rs9486409
• NM_001371242.2:c.*3225A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371242.2(CRYBG1):​c.*3225A>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 0.00000294 in 339,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CRYBG1 NM_001371242.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 0 publications found

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]

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), Ambry Genetics, G2P
• autosomal recessive optic atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371242.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG1	NM_001371242.2	MANE Select	c.*3225A>C		3_prime_UTR	Exon 22 of 22	NP_001358171.1	Q9Y4K1-3
	RTN4IP1	NM_032730.5	MANE Select	c.*205T>G		3_prime_UTR	Exon 9 of 9	NP_116119.2	Q8WWV3-1
	CRYBG1	NM_001624.4		c.*3225A>C		3_prime_UTR	Exon 20 of 20	NP_001615.2	Q9Y4K1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG1	ENST00000633556.3	TSL:5 MANE Select	c.*3225A>C		3_prime_UTR	Exon 22 of 22	ENSP00000488010.2	Q9Y4K1-3
	RTN4IP1	ENST00000369063.8	TSL:1 MANE Select	c.*205T>G		3_prime_UTR	Exon 9 of 9	ENSP00000358059.3	Q8WWV3-1
	RTN4IP1	ENST00000865782.1		c.*205T>G		downstream_gene	N/A	ENSP00000535841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000294 AC: 1 AN: 339606 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 179458

African (AFR) AF: 0.00 AC: 0 AN: 8960

American (AMR) AF: 0.00 AC: 0 AN: 12240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10792

East Asian (EAS) AF: 0.00 AC: 0 AN: 24156

South Asian (SAS) AF: 0.00 AC: 0 AN: 30552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1452

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 208524

Other (OTH) AF: 0.0000507 AC: 1 AN: 19742

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs9486409; hg19: chr6-107019666;