rs6940766

Variant names:

• chr6-83905785-G-A
• rs6940766
• NM_016230.4:c.331-3224G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016230.4. 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
	CYB5R4	NM_016230.4	MANE Select	c.331-3224G>A		intron	N/A	NP_057314.2
	RIPPLY2-CYB5R4	NM_001400774.1		c.229-3224G>A		intron	N/A	NP_001387703.1
	RIPPLY2-CYB5R4	NR_174603.1		n.490-3224G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R4	ENST00000369681.10	TSL:1 MANE Select	c.331-3224G>A		intron	N/A	ENSP00000358695.3
	CYB5R4	ENST00000369679.4	TSL:3	c.229-3224G>A		intron	N/A	ENSP00000358693.4

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

African (AFR) AF: 0.727 AC: 30052 AN: 41346

American (AMR) AF: 0.260 AC: 3964 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0834 AC: 289 AN: 3464

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5166

South Asian (SAS) AF: 0.0663 AC: 320 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10578

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5535 AN: 67964

Other (OTH) AF: 0.233 AC: 491 AN: 2110

Alfa AF: 0.242 Hom.: 1440

Bravo AF: 0.320

Asia WGS AF: 0.176 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6940766; hg19: chr6-84615504;