Variant 17-76528584-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_134268.5(CYGB):c.567G>A(p.Gly189Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,287,306 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 8 hom. )

Consequence

CYGB
NM_134268.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.760

Variant links:

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]

CYGB links:

PRCD (HGNC:):

PRCD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077679455).

BP6

Variant 17-76528584-C-T is Benign according to our data. Variant chr17-76528584-C-T is described in ClinVar as [Benign]. Clinvar id is 771500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00293 (446/152332) while in subpopulation AMR AF= 0.0283 (433/15278). AF 95% confidence interval is 0.0261. There are 10 homozygotes in gnomad4. There are 292 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYGB	NM_134268.5 linkuse as main transcript	c.567G>A	p.Gly189Gly	synonymous_variant	4/4	ENST00000293230.10	NP_599030.1	Q8WWM9A0A1K0FUB6
PRCD	NR_033357.2 linkuse as main transcript	n.248+751C>T		intron_variant
CYGB	XM_005257005.4 linkuse as main transcript	c.*1368G>A		downstream_gene_variant			XP_005257062.1
CYGB	XM_017024116.2 linkuse as main transcript	c.*1368G>A		downstream_gene_variant			XP_016879605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYGB	ENST00000293230.10 linkuse as main transcript	c.567G>A	p.Gly189Gly	synonymous_variant	4/4	1	NM_134268.5	ENSP00000293230.4		Q8WWM9

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00143

AC:

AN:

48948

Hom.:

AF XY:

0.00146

AC XY:

AN XY:

23916

show subpopulations

Gnomad AFR exome

AF:

0.000467

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000388

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.000315

AC:

358

AN:

1134974

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

155

AN XY:

541840

show subpopulations

Gnomad4 AFR exome

AF:

0.000291

Gnomad4 AMR exome

AF:

0.0298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000368

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000531

Gnomad4 OTH exome

AF:

0.000903

GnomAD4 genome

AF:

0.00293

AC:

446

AN:

152332

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00379

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00189

AC:

220

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

DANN

Benign

0.84

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0078

Sift4G

Benign

0.24

Vest4

0.29

MVP

0.94

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over