rs1998742

Variant names:

• chr6-83912897-G-A
• rs1998742
• NM_016230.4:c.413-1519G>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.413-1519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,044 control chromosomes in the GnomAD database, including 3,778 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 0.20 (3778 hom., cov: 32)
• Consequence: CYB5R4 NM_016230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYB5R4	NM_016230.4	c.413-1519G>A		intron_variant	Intron 4 of 15	ENST00000369681.10	NP_057314.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5R4	ENST00000369681.10	c.413-1519G>A		intron_variant	Intron 4 of 15	1	NM_016230.4	ENSP00000358695.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29697 AN: 151926 Hom.: 3782 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.195 AC: 29686 AN: 152044 Hom.: 3778 Cov.: 32 AF XY: 0.203 AC XY: 15064 AN XY: 74316

African (AFR) AF: 0.0520 AC: 2158 AN: 41510

American (AMR) AF: 0.139 AC: 2131 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1847 AN: 5164

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.357 AC: 3764 AN: 10548

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.247 AC: 16761 AN: 67936

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.211 Hom.: 4010

Bravo AF: 0.170

Asia WGS AF: 0.297 AC: 1029 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.060
PhyloP100		-0.81
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: rs1998742; hg19: chr6-84622616;