rs1470114558

Variant names:

• chr6-83924488-T-C
• rs1470114558
• NM_016230.4:c.710T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-83924488-T-C
• chr6-83924488-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016230.4(CYB5R4):​c.710T>C​(p.Val237Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V237G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYB5R4 NM_016230.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09744176).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R4	NM_016230.4	MANE Select	c.710T>C	p.Val237Ala	missense	Exon 10 of 16	NP_057314.2	Q7L1T6
	RIPPLY2-CYB5R4	NM_001400774.1		c.608T>C	p.Val203Ala	missense	Exon 11 of 17	NP_001387703.1	B2R7W7
	RIPPLY2-CYB5R4	NR_174603.1		n.869T>C		non_coding_transcript_exon	Exon 11 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R4	ENST00000369681.10	TSL:1 MANE Select	c.710T>C	p.Val237Ala	missense	Exon 10 of 16	ENSP00000358695.3	Q7L1T6
	CYB5R4	ENST00000942770.1		c.728T>C	p.Val243Ala	missense	Exon 10 of 16	ENSP00000612829.1
	CYB5R4	ENST00000942768.1		c.710T>C	p.Val237Ala	missense	Exon 10 of 16	ENSP00000612827.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.81
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.12
Sift	Benign	0.56	T
Sift4G	Benign	0.18	T
Polyphen		0.0090	B
Vest4		0.23
MutPred		0.56		Loss of helix (P = 0.0068)
MVP		0.41
MPC		0.36
ClinPred		0.79	D
GERP RS		4.7
Varity_R		0.10
gMVP		0.54
Mutation Taster		=74/26	polymorphism

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: rs1470114558; hg19: chr6-84634207;