NM_001371242.2:c.*3194A>G

Variant names:

• chr6-106571760-A-G
• rs9320183
• NM_001371242.2:c.*3194A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: Benign. The variant received -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 VariationId 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.

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.*3194A>G		3_prime_UTR	Exon 22 of 22	NP_001358171.1	Q9Y4K1-3
	RTN4IP1	NM_032730.5	MANE Select	c.*236T>C		3_prime_UTR	Exon 9 of 9	NP_116119.2	Q8WWV3-1
	CRYBG1	NM_001624.4		c.*3194A>G		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.*3194A>G		3_prime_UTR	Exon 22 of 22	ENSP00000488010.2	Q9Y4K1-3
	RTN4IP1	ENST00000369063.8	TSL:1 MANE Select	c.*236T>C		3_prime_UTR	Exon 9 of 9	ENSP00000358059.3	Q8WWV3-1
	RTN4IP1	ENST00000865782.1		c.*236T>C		downstream_gene	N/A	ENSP00000535841.1

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

African (AFR) AF: 0.175 AC: 1381 AN: 7894

American (AMR) AF: 0.105 AC: 1133 AN: 10810

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1065 AN: 9428

East Asian (EAS) AF: 0.115 AC: 2240 AN: 19530

South Asian (SAS) AF: 0.127 AC: 3935 AN: 30922

European-Finnish (FIN) AF: 0.0893 AC: 1656 AN: 18542

Middle Eastern (MID) AF: 0.157 AC: 196 AN: 1252

European-Non Finnish (NFE) AF: 0.0899 AC: 16507 AN: 183616

Other (OTH) AF: 0.104 AC: 1805 AN: 17388

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

African (AFR) AF: 0.206 AC: 8571 AN: 41538

American (AMR) AF: 0.126 AC: 1929 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3472

East Asian (EAS) AF: 0.142 AC: 735 AN: 5184

South Asian (SAS) AF: 0.132 AC: 636 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10610

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7476 AN: 68016

Other (OTH) AF: 0.155 AC: 328 AN: 2110

Alfa AF: 0.126 Hom.: 1619

Bravo AF: 0.145

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.37
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9320183; hg19: chr6-107019635;