6-106571786-T-C

Variant names:

• chr6-106571786-T-C
• rs9486408
• NM_001371242.2:c.*3220T>C

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.*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
• Publications: 5 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=-0.96).
• BP6: Variant 6-106571786-T-C is Benign according to our data. Variant chr6-106571786-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.*3220T>C		3_prime_UTR	Exon 22 of 22	NP_001358171.1	Q9Y4K1-3
	RTN4IP1	NM_032730.5	MANE Select	c.*210A>G		3_prime_UTR	Exon 9 of 9	NP_116119.2	Q8WWV3-1
	CRYBG1	NM_001624.4		c.*3220T>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.*3220T>C		3_prime_UTR	Exon 22 of 22	ENSP00000488010.2	Q9Y4K1-3
	RTN4IP1	ENST00000369063.8	TSL:1 MANE Select	c.*210A>G		3_prime_UTR	Exon 9 of 9	ENSP00000358059.3	Q8WWV3-1
	RTN4IP1	ENST00000865782.1		c.*210A>G		downstream_gene	N/A	ENSP00000535841.1

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

African (AFR) AF: 0.253 AC: 2173 AN: 8596

American (AMR) AF: 0.113 AC: 1339 AN: 11858

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 1274 AN: 10408

East Asian (EAS) AF: 0.128 AC: 2945 AN: 23070

South Asian (SAS) AF: 0.125 AC: 3785 AN: 30330

European-Finnish (FIN) AF: 0.0959 AC: 2118 AN: 22092

Middle Eastern (MID) AF: 0.178 AC: 250 AN: 1408

European-Non Finnish (NFE) AF: 0.0964 AC: 19501 AN: 202278

Other (OTH) AF: 0.117 AC: 2240 AN: 19140

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

African (AFR) AF: 0.281 AC: 11630 AN: 41438

American (AMR) AF: 0.131 AC: 2004 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3466

East Asian (EAS) AF: 0.142 AC: 734 AN: 5180

South Asian (SAS) AF: 0.132 AC: 635 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1289 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7471 AN: 68000

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.129 Hom.: 689

Bravo AF: 0.169

Asia WGS AF: 0.155 AC: 542 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	-0.96
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-1.9
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: rs9486408; hg19: chr6-107019661; COSMIC: COSV107457579; COSMIC: COSV107457579;