rs6940766

chr6-83905785-G-A

Variant summary

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

The NM_016230.4(CYB5R4):c.331-3224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,928 control chromosomes in the GnomAD database, including 12,178 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 0.29 (12178 hom., cov: 32)
• Consequence: CYB5R4 NM_016230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R4	NM_016230.4	c.331-3224G>A		intron_variant		ENST00000369681.10
RIPPLY2-CYB5R4	NR_174604.1	n.552-3224G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R4	ENST00000369681.10	c.331-3224G>A		intron_variant		1	NM_016230.4	P1
CYB5R4	ENST00000369679.4	c.229-3224G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43242 AN: 151810 Hom.: 12130 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.0834

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.285 AC: 43361 AN: 151928 Hom.: 12178 Cov.: 32 AF XY: 0.283 AC XY: 20994 AN XY: 74262

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.0834

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.233

Alfa AF: 0.225 Hom.: 1236

Bravo AF: 0.320

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.1
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6940766; hg19: chr6-84615504;