19-3769896-CCTGG-C

Position:

• chr19-3769896-CCTGG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001319074.4(RAX2):​c.*721_*724delCCAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,862 control chromosomes in the GnomAD database, including 823 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (823 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (0 hom.)
• Consequence: RAX2 NM_001319074.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.662

Genes affected

RAX2 (HGNC:18286): (retina and anterior neural fold homeobox 2) This gene encodes a homeodomain-containing protein that plays a role in eye development. Mutation of this gene causes age-related macular degeneration type 6, an eye disorder resulting in accumulations of protein and lipid beneath the retinal pigment epithelium and within the Bruch's membrane. Defects in this gene can also cause cone-rod dystrophy type 11, a disease characterized by the initial degeneration of cone photoreceptor cells and resulting in loss of color vision and visual acuity, followed by the degeneration of rod photoreceptor cells, which progresses to night blindness and the loss of peripheral vision. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-3769896-CCTGG-C is Benign according to our data. Variant chr19-3769896-CCTGG-C is described in ClinVar as [Benign]. Clinvar id is 328954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAX2	NM_001319074.4	c.*721_*724delCCAG		3_prime_UTR_variant	3/3	ENST00000555633.3	NP_001306003.2
RAX2	NM_032753.4	c.*721_*724delCCAG		3_prime_UTR_variant	3/3		NP_116142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAX2	ENST00000555633	c.*721_*724delCCAG		3_prime_UTR_variant	3/3	1	NM_001319074.4	ENSP00000450456.3
RAX2	ENST00000555978	c.*721_*724delCCAG		3_prime_UTR_variant	3/3	1		ENSP00000450687.2

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9413 AN: 152078 Hom.: 823 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00756

Gnomad OTH AF: 0.0522

GnomAD4 exome AF: 0.00751 AC: 5 AN: 666 Hom.: 0 AF XY: 0.00980 AC XY: 5 AN XY: 510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.00722

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0619 AC: 9416 AN: 152196 Hom.: 823 Cov.: 32 AF XY: 0.0604 AC XY: 4496 AN XY: 74416

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.00756

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0421 Hom.: 61

Bravo AF: 0.0693

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Macular degeneration Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cone-Rod Dystrophy, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs138512126; hg19: chr19-3769894;