rs79588413

Variant names:

• chr19-3770967-G-A
• rs79588413
• NM_001319074.4:c.217-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3770967-G-A
• chr19-3770967-G-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.217-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,550,918 control chromosomes in the GnomAD database, including 23,436 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1885 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21551 hom.)
• Consequence: RAX2 NM_001319074.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005479
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.18
• Publications: 7 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=-0.83).
• BP6: Variant 19-3770967-G-A is Benign according to our data. Variant chr19-3770967-G-A is described in ClinVar as Benign. ClinVar VariationId is 96230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 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.217-8C>T		splice_region intron	N/A	NP_001306003.2	Q96IS3
	RAX2	NM_032753.4		c.217-8C>T		splice_region intron	N/A	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.217-8C>T		splice_region intron	N/A	ENSP00000450456.3	Q96IS3
	RAX2	ENST00000555978.5	TSL:1	c.217-8C>T		splice_region intron	N/A	ENSP00000450687.2	Q96IS3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23000 AN: 152068 Hom.: 1884 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.158 AC: 24393 AN: 154002 AF XY: 0.163

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0206

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.172 AC: 240457 AN: 1398732 Hom.: 21551 Cov.: 30 AF XY: 0.172 AC XY: 118949 AN XY: 692290

African (AFR) AF: 0.123 AC: 4009 AN: 32564

American (AMR) AF: 0.130 AC: 4885 AN: 37680

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3986 AN: 25318

East Asian (EAS) AF: 0.0281 AC: 1060 AN: 37698

South Asian (SAS) AF: 0.159 AC: 12920 AN: 81208

European-Finnish (FIN) AF: 0.161 AC: 5548 AN: 34456

Middle Eastern (MID) AF: 0.214 AC: 1175 AN: 5500

European-Non Finnish (NFE) AF: 0.182 AC: 197225 AN: 1085808

Other (OTH) AF: 0.165 AC: 9649 AN: 58500

GnomAD4 genome AF: 0.151 AC: 23018 AN: 152186 Hom.: 1885 Cov.: 33 AF XY: 0.150 AC XY: 11186 AN XY: 74402

African (AFR) AF: 0.121 AC: 5007 AN: 41522

American (AMR) AF: 0.138 AC: 2108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5170

South Asian (SAS) AF: 0.155 AC: 751 AN: 4830

European-Finnish (FIN) AF: 0.156 AC: 1655 AN: 10618

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

European-Non Finnish (NFE) AF: 0.180 AC: 12229 AN: 67968

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.169 Hom.: 411

Bravo AF: 0.150

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Age related macular degeneration 6 (1)
-	-	1	Cone-rod dystrophy 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.92
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0060
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: rs79588413; hg19: chr19-3770965;