NM_001319074.4:c.*866C>T

Variant names:

• chr19-3769755-G-A
• rs917545
• NM_001319074.4:c.*866C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001319074.4(RAX2):​c.*866C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 153,164 control chromosomes in the GnomAD database, including 48,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47703 hom., cov: 33)
  • Exomes 𝑓: 0.78 (315 hom.)
• Consequence: RAX2 NM_001319074.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.08
• Publications: 3 publications found

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]

RAX2 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Franklin by Genoox
• cone-rod dystrophy 11

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 95

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-3769755-G-A is Benign according to our data. Variant chr19-3769755-G-A is described in ClinVar as Benign. ClinVar VariationId is 328952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319074.4. 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
	RAX2	NM_001319074.4	MANE Select	c.*866C>T		3_prime_UTR	Exon 3 of 3	NP_001306003.2	Q96IS3
	RAX2	NM_032753.4		c.*866C>T		3_prime_UTR	Exon 3 of 3	NP_116142.1	Q96IS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAX2	ENST00000555633.3	TSL:1 MANE Select	c.*866C>T		3_prime_UTR	Exon 3 of 3	ENSP00000450456.3	Q96IS3
	RAX2	ENST00000555978.5	TSL:1	c.*866C>T		3_prime_UTR	Exon 3 of 3	ENSP00000450687.2	Q96IS3

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120281 AN: 152048 Hom.: 47667 Cov.: 33

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.781 AC: 779 AN: 998 Hom.: 315 Cov.: 0 AF XY: 0.782 AC XY: 593 AN XY: 758

African (AFR) AF: 0.700 AC: 7 AN: 10

American (AMR) AF: 0.750 AC: 6 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.875 AC: 28 AN: 32

South Asian (SAS) AF: 0.823 AC: 51 AN: 62

European-Finnish (FIN) AF: 0.737 AC: 28 AN: 38

Middle Eastern (MID) AF: 0.667 AC: 4 AN: 6

European-Non Finnish (NFE) AF: 0.776 AC: 618 AN: 796

Other (OTH) AF: 0.825 AC: 33 AN: 40

GnomAD4 genome AF: 0.791 AC: 120369 AN: 152166 Hom.: 47703 Cov.: 33 AF XY: 0.789 AC XY: 58698 AN XY: 74382

African (AFR) AF: 0.840 AC: 34887 AN: 41530

American (AMR) AF: 0.783 AC: 11966 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3472

East Asian (EAS) AF: 0.839 AC: 4339 AN: 5170

South Asian (SAS) AF: 0.823 AC: 3968 AN: 4824

European-Finnish (FIN) AF: 0.705 AC: 7459 AN: 10582

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52654 AN: 67988

Other (OTH) AF: 0.782 AC: 1651 AN: 2110

Alfa AF: 0.733 Hom.: 3383

Bravo AF: 0.798

Asia WGS AF: 0.853 AC: 2968 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Age related macular degeneration 6 (1)
-	-	1	Cone-rod dystrophy 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs917545; hg19: chr19-3769753;