chr6-83939418-A-G

Position:

• chr6-83939418-A-G

Variant summary

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

The NM_016230.4(CYB5R4):​c.1109-638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,118 control chromosomes in the GnomAD database, including 12,211 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 (12211 hom., cov: 32)
• Consequence: CYB5R4 NM_016230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

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=-0.91).
• 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	Protein	UniProt
CYB5R4	NM_016230.4	c.1109-638A>G		intron_variant		ENST00000369681.10	NP_057314.2
RIPPLY2-CYB5R4	NR_174604.1	n.1330-638A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5R4	ENST00000369681.10	c.1109-638A>G		intron_variant		1	NM_016230.4	ENSP00000358695	P1
CYB5R4	ENST00000479164.1	n.449-638A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43436 AN: 152000 Hom.: 12162 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.286 AC: 43556 AN: 152118 Hom.: 12211 Cov.: 32 AF XY: 0.284 AC XY: 21135 AN XY: 74378

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.233

Alfa AF: 0.0562 Hom.: 67

Bravo AF: 0.320

Asia WGS AF: 0.184 AC: 640 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.50

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: rs1325469; hg19: chr6-84649137; COSMIC: COSV63751008;