rs9353149

Positions:

• chr6-83884828-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016230.4(CYB5R4):​c.230-8694T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,092 control chromosomes in the GnomAD database, including 8,044 homozygotes. 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: 𝑓 0.24 (8044 hom., cov: 33)
• Consequence: CYB5R4 NM_016230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

Genes affected

CYB5R4 (HGNC:20147): (cytochrome b5 reductase 4) NCB5OR is a flavohemoprotein that contains functional domains found in both cytochrome b5 (CYB5A; MIM 613218) and CYB5 reductase (CYB5R3; MIM 613213) (Zhu et al., 1999 [PubMed 10611283]).[supplied by OMIM, Jan 2010]

RIPPLY2-CYB5R4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5R4	NM_016230.4	c.230-8694T>G		intron_variant		ENST00000369681.10	NP_057314.2
RIPPLY2-CYB5R4	NR_174604.1	n.451-8694T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R4	ENST00000369681.10	c.230-8694T>G		intron_variant		1	NM_016230.4	ENSP00000358695	P1
CYB5R4	ENST00000369679.4	c.128-8694T>G		intron_variant		3		ENSP00000358693

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36734 AN: 151972 Hom.: 8010 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.242 AC: 36835 AN: 152092 Hom.: 8044 Cov.: 33 AF XY: 0.241 AC XY: 17898 AN XY: 74372

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.196

Alfa AF: 0.108 Hom.: 2616

Bravo AF: 0.271

Asia WGS AF: 0.166 AC: 579 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs9353149; hg19: chr6-84594547;