chr17-76528280-G-T

Variant names:

• chr17-76528280-G-T
• rs1052143
• NM_134268.5:c.*298C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_134268.5(CYGB):​c.*298C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYGB NM_134268.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 2 publications found

Genes affected

CYGB (HGNC:16505): (cytoglobin) This gene encodes a globin protein found in vertebrate cells. The encoded protein is described as a hexacoordinate hemoglobin which binds ligand differently from the pentacoordinate hemoglobins involved in oxygen transport, and may be involved in protection during oxidative stress. This gene is located on chromosome 17 in the same region as a retinal gene which is mutated in progressive rod-cone degeneration, but in the opposite orientation. [provided by RefSeq, Jan 2012]

PRCD (HGNC:32528): (photoreceptor disc component) This gene is predominantly expressed in the retina, and mutations in this gene are the cause of autosomal recessive retinal degeneration in both humans and dogs. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

PRCD Gene-Disease associations (from GenCC):

• retinitis pigmentosa 36

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134268.5. 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
	CYGB	NM_134268.5	MANE Select	c.*298C>A		3_prime_UTR	Exon 4 of 4	NP_599030.1	Q8WWM9
	PRCD	NR_033357.2		n.248+447G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYGB	ENST00000293230.10	TSL:1 MANE Select	c.*298C>A		3_prime_UTR	Exon 4 of 4	ENSP00000293230.4	Q8WWM9
	PRCD	ENST00000397633.7	TSL:1	n.45+447G>T		intron	N/A
	CYGB	ENST00000586160.1	TSL:3	n.619C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 248022 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125972

African (AFR) AF: 0.00 AC: 0 AN: 7184

American (AMR) AF: 0.00 AC: 0 AN: 7476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9258

East Asian (EAS) AF: 0.00 AC: 0 AN: 22910

South Asian (SAS) AF: 0.00 AC: 0 AN: 3516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159008

Other (OTH) AF: 0.00 AC: 0 AN: 16430

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.75
PhyloP100		0.56

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: rs1052143; hg19: chr17-74524362;