rs149445684

Variant names:

• chr1-54179172-G-C
• rs149445684
• NM_001031672.4:c.721C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-54179172-G-C
• chr1-54179172-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001031672.4(CYB5RL):​c.721C>G​(p.Arg241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R241H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CYB5RL NM_001031672.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

CYB5RL (HGNC:32220): (cytochrome b5 reductase like) Predicted to enable cytochrome-b5 reductase activity, acting on NAD(P)H. Predicted to be involved in bicarbonate transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256407 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031672.4. 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
	CYB5RL	NM_001031672.4	MANE Select	c.721C>G	p.Arg241Gly	missense	Exon 7 of 8	NP_001026842.2	Q6IPT4-1
	CYB5RL	NM_001353353.2		c.484C>G	p.Arg162Gly	missense	Exon 5 of 6	NP_001340282.1
	CYB5RL	NM_001353354.2		c.277C>G	p.Arg93Gly	missense	Exon 6 of 7	NP_001340283.1	Q6IPT4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5RL	ENST00000534324.6	TSL:5 MANE Select	c.721C>G	p.Arg241Gly	missense	Exon 7 of 8	ENSP00000434343.1	Q6IPT4-1
	CYB5RL	ENST00000420054.5	TSL:1	n.*715C>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000403021.1	F8WDU4
	CYB5RL	ENST00000421415.5	TSL:1	n.*359C>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000394709.1	F8VW03

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 247656 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460818 Hom.: 0 Cov.: 31 AF XY: 0.00000964 AC XY: 7 AN XY: 726516

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000448 AC: 2 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111632

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

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	0.21
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.64
Sift	Benign	0.19	T
Sift4G	Uncertain	0.033	D
Polyphen		0.65	P
Vest4		0.79
MutPred		0.66		Loss of sheet (P = 0.0817)
MVP		0.68
ClinPred		0.79	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.66
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149445684; hg19: chr1-54644845;