6-83889625-C-G

Variant names:

• chr6-83889625-C-G
• rs2324482
• NM_016230.4:c.230-3897C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016230.4(CYB5R4):​c.230-3897C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,178 control chromosomes in the GnomAD database, including 3,533 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 0.15 (3533 hom., cov: 32)
• Consequence: CYB5R4 NM_016230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 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.230-3897C>G		intron	N/A	NP_057314.2
	RIPPLY2-CYB5R4	NM_001400774.1		c.128-3897C>G		intron	N/A	NP_001387703.1
	RIPPLY2-CYB5R4	NR_174603.1		n.389-3897C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R4	ENST00000369681.10	TSL:1 MANE Select	c.230-3897C>G		intron	N/A	ENSP00000358695.3
	CYB5R4	ENST00000942770.1		c.230-3897C>G		intron	N/A	ENSP00000612829.1
	CYB5R4	ENST00000942768.1		c.230-3897C>G		intron	N/A	ENSP00000612827.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23394 AN: 152060 Hom.: 3527 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.154 AC: 23456 AN: 152178 Hom.: 3533 Cov.: 32 AF XY: 0.155 AC XY: 11537 AN XY: 74392

African (AFR) AF: 0.375 AC: 15553 AN: 41488

American (AMR) AF: 0.199 AC: 3045 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1341 AN: 5162

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4832

European-Finnish (FIN) AF: 0.0523 AC: 555 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2330 AN: 68000

Other (OTH) AF: 0.124 AC: 262 AN: 2114

Alfa AF: 0.0124 Hom.: 5

Bravo AF: 0.180

Asia WGS AF: 0.150 AC: 522 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	0.38
DANN	Benign	0.60
PhyloP100		-1.7
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: rs2324482; hg19: chr6-84599344;