chr12-55721801-C-T

Variant names:

• chr12-55721801-C-T
• rs3138142
• NM_002905.5:c.423C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002905.5(RDH5):​c.423C>T​(p.Ile141Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,824 control chromosomes in the GnomAD database, including 41,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2531 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38528 hom.)
• Consequence: RDH5 NM_002905.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.74
• Publications: 42 publications found

Genes affected

RDH5 (HGNC:9940): (retinol dehydrogenase 5) This gene encodes an enzyme belonging to the short-chain dehydrogenases/reductases (SDR) family. This retinol dehydrogenase functions to catalyze the final step in the biosynthesis of 11-cis retinaldehyde, which is the universal chromophore of visual pigments. Mutations in this gene cause autosomal recessive fundus albipunctatus, a rare form of night blindness that is characterized by a delay in the regeneration of cone and rod photopigments. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S1 (biogenesis of lysosomal organelles complex-1, subunit 1) gene. [provided by RefSeq, Dec 2010]

RDH5 Gene-Disease associations (from GenCC):

• RDH5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• fundus albipunctatus

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000258311 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 12-55721801-C-T is Benign according to our data. Variant chr12-55721801-C-T is described in ClinVar as Benign. ClinVar VariationId is 258857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002905.5. 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
	RDH5	NM_002905.5	MANE Select	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 5	NP_002896.2	Q92781
	RDH5	NM_001199771.3		c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 5	NP_001186700.1	Q92781
	BLOC1S1-RDH5	NR_037658.1		n.482C>T		non_coding_transcript_exon	Exon 4 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH5	ENST00000257895.10	TSL:1 MANE Select	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 5	ENSP00000257895.6	Q92781
	RDH5	ENST00000548082.1	TSL:1	c.423C>T	p.Ile141Ile	synonymous	Exon 3 of 5	ENSP00000447128.1	Q92781
	ENSG00000258311	ENST00000550412.5	TSL:2	c.*95C>T		3_prime_UTR	Exon 4 of 4	ENSP00000447650.1	F8W036

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24249 AN: 152058 Hom.: 2535 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.191 AC: 47634 AN: 250026 AF XY: 0.206

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.223 AC: 325747 AN: 1461648 Hom.: 38528 Cov.: 35 AF XY: 0.227 AC XY: 165306 AN XY: 727118

African (AFR) AF: 0.0359 AC: 1202 AN: 33480

American (AMR) AF: 0.0932 AC: 4170 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5799 AN: 26136

East Asian (EAS) AF: 0.0813 AC: 3229 AN: 39700

South Asian (SAS) AF: 0.329 AC: 28374 AN: 86252

European-Finnish (FIN) AF: 0.165 AC: 8778 AN: 53258

Middle Eastern (MID) AF: 0.240 AC: 1381 AN: 5762

European-Non Finnish (NFE) AF: 0.233 AC: 259627 AN: 1111946

Other (OTH) AF: 0.218 AC: 13187 AN: 60394

GnomAD4 genome AF: 0.159 AC: 24225 AN: 152176 Hom.: 2531 Cov.: 32 AF XY: 0.158 AC XY: 11760 AN XY: 74404

African (AFR) AF: 0.0403 AC: 1675 AN: 41542

American (AMR) AF: 0.133 AC: 2026 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3466

East Asian (EAS) AF: 0.108 AC: 554 AN: 5152

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1604 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15256 AN: 67996

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.186 Hom.: 4210

Bravo AF: 0.148

Asia WGS AF: 0.224 AC: 779 AN: 3478

EpiCase AF: 0.225

EpiControl AF: 0.220

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Pigmentary retinal dystrophy (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		-1.7
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: rs3138142; hg19: chr12-56115585; COSMIC: COSV57676409; COSMIC: COSV57676409;