rs2232842

Positions:

• chr1-202966783-T-A
• chr1-202966783-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016243.3(CYB5R1):​c.131A>T​(p.Asn44Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N44S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYB5R1 NM_016243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.890

Genes affected

CYB5R1 (HGNC:13397): (cytochrome b5 reductase 1) Predicted to enable FAD binding activity. Predicted to be involved in bicarbonate transport. Located in extracellular exosome; membrane; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5R1	NM_016243.3	c.131A>T	p.Asn44Ile	missense_variant	2/9	ENST00000367249.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5R1	ENST00000367249.9	c.131A>T	p.Asn44Ile	missense_variant	2/9	1	NM_016243.3	P1
CYB5R1	ENST00000473599.5	n.201A>T		non_coding_transcript_exon_variant	2/5	3
CYB5R1	ENST00000478009.1	n.151A>T		non_coding_transcript_exon_variant	2/3	2
CYB5R1	ENST00000482572.5	n.169A>T		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.070	D
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	0.038	P
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.32
Sift	Benign	0.088	T
Sift4G	Benign	0.076	T
Polyphen		0.036	B
Vest4		0.40
MutPred		0.45		Loss of solvent accessibility (P = 0.0509);
MVP		0.87
MPC		0.24
ClinPred		0.77	D
GERP RS		3.4
Varity_R		0.24
gMVP		0.75

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: rs2232842; hg19: chr1-202935911;