rs917547

Variant names:

• chr19-3769901-C-T
• rs917547
• NM_001319074.4:c.*720G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3769901-C-T
• chr19-3769901-C-A

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.*720G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 137,626 control chromosomes in the GnomAD database, including 1,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1827 hom., cov: 32)
  • Exomes 𝑓: 0.13 (9 hom.)
• Consequence: RAX2 NM_001319074.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.631
• Publications: 4 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 19-3769901-C-T is Benign according to our data. Variant chr19-3769901-C-T is described in ClinVar as Benign. ClinVar VariationId is 328955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 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.*720G>A		3_prime_UTR	Exon 3 of 3	NP_001306003.2	Q96IS3
	RAX2	NM_032753.4		c.*720G>A		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.*720G>A		3_prime_UTR	Exon 3 of 3	ENSP00000450456.3	Q96IS3
	RAX2	ENST00000555978.5	TSL:1	c.*720G>A		3_prime_UTR	Exon 3 of 3	ENSP00000450687.2	Q96IS3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 22616 AN: 136944 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.125 AC: 71 AN: 568 Hom.: 9 Cov.: 0 AF XY: 0.133 AC XY: 56 AN XY: 420

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.0417 AC: 1 AN: 24

European-Finnish (FIN) AF: 0.0909 AC: 2 AN: 22

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.140 AC: 65 AN: 464

Other (OTH) AF: 0.100 AC: 3 AN: 30

GnomAD4 genome AF: 0.165 AC: 22635 AN: 137058 Hom.: 1827 Cov.: 32 AF XY: 0.164 AC XY: 11011 AN XY: 67196

African (AFR) AF: 0.162 AC: 4644 AN: 28588

American (AMR) AF: 0.146 AC: 2125 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 562 AN: 3410

East Asian (EAS) AF: 0.0256 AC: 133 AN: 5186

South Asian (SAS) AF: 0.155 AC: 745 AN: 4804

European-Finnish (FIN) AF: 0.161 AC: 1648 AN: 10258

Middle Eastern (MID) AF: 0.205 AC: 55 AN: 268

European-Non Finnish (NFE) AF: 0.182 AC: 12198 AN: 67128

Other (OTH) AF: 0.180 AC: 347 AN: 1930

Alfa AF: 0.160 Hom.: 248

Bravo AF: 0.148

Asia WGS AF: 0.0940 AC: 326 AN: 3446

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	5.8
DANN	Benign	0.90
PhyloP100		-0.63
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: rs917547; hg19: chr19-3769899;