chr12-55720985-G-C

Variant names:

• chr12-55720985-G-C
• rs3138144
• NM_002905.5:c.-32-168G>C

Variant summary

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

The NM_002905.5(RDH5):​c.-32-168G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,898 control chromosomes in the GnomAD database, including 12,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.38 (12398 hom., cov: 32)
• Consequence: RDH5 NM_002905.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.193
• Publications: 31 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):

• fundus albipunctatus

  Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• RDH5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000258311 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-55720985-G-C is Benign according to our data. Variant chr12-55720985-G-C is described in ClinVar as Benign. ClinVar VariationId is 1266740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH5	NM_002905.5	MANE Select	c.-32-168G>C		intron	N/A	NP_002896.2
	RDH5	NM_001199771.3		c.-37-163G>C		intron	N/A	NP_001186700.1
	BLOC1S1-RDH5	NR_037658.1		n.370-704G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH5	ENST00000257895.10	TSL:1 MANE Select	c.-32-168G>C		intron	N/A	ENSP00000257895.6
	RDH5	ENST00000548082.1	TSL:1	c.-37-163G>C		intron	N/A	ENSP00000447128.1
	ENSG00000258311	ENST00000550412.5	TSL:2	c.352-704G>C		intron	N/A	ENSP00000447650.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56962 AN: 151784 Hom.: 12400 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56962 AN: 151898 Hom.: 12398 Cov.: 32 AF XY: 0.376 AC XY: 27933 AN XY: 74242

African (AFR) AF: 0.142 AC: 5865 AN: 41406

American (AMR) AF: 0.403 AC: 6147 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2233 AN: 5174

South Asian (SAS) AF: 0.554 AC: 2667 AN: 4818

European-Finnish (FIN) AF: 0.459 AC: 4821 AN: 10498

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32094 AN: 67962

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.312 Hom.: 1048

Bravo AF: 0.357

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		0.19
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: rs3138144; hg19: chr12-56114769; COSMIC: COSV57676044; COSMIC: COSV57676044;