19-3769528-GGTGATCTGGGA-G

Position:

• chr19-3769528-GGTGATCTGGGA-G

Variant summary

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

The NM_001319074.4(RAX2):​c.*1082_*1092delTCCCAGATCAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,692 control chromosomes in the GnomAD database, including 278 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (278 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (0 hom.)
• Consequence: RAX2 NM_001319074.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.472

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 19-3769528-GGTGATCTGGGA-G is Benign according to our data. Variant chr19-3769528-GGTGATCTGGGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 328947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAX2	NM_001319074.4	c.*1082_*1092delTCCCAGATCAC		3_prime_UTR_variant	3/3	ENST00000555633.3	NP_001306003.2
RAX2	NM_032753.4	c.*1082_*1092delTCCCAGATCAC		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.*1082_*1092delTCCCAGATCAC		3_prime_UTR_variant	3/3	1	NM_001319074.4	ENSP00000450456.3
RAX2	ENST00000555978	c.*1082_*1092delTCCCAGATCAC		3_prime_UTR_variant	3/3	1		ENSP00000450687.2

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5794 AN: 152140 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00726

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.00461 AC: 2 AN: 434 Hom.: 0 AF XY: 0.00667 AC XY: 2 AN XY: 300

Gnomad4 AFR 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: 0.00

Gnomad4 NFE exome AF: 0.00654

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0381 AC: 5795 AN: 152258 Hom.: 278 Cov.: 32 AF XY: 0.0375 AC XY: 2790 AN XY: 74450

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.00726

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0275 Hom.: 12

Bravo AF: 0.0418

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-Rod Dystrophy, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Macular degeneration Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143816706; hg19: chr19-3769526;