1-54179589-T-C

Variant summary

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

The NM_001031672.4(CYB5RL):c.541-237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,096 control chromosomes in the GnomAD database, including 34,152 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 0.66 (34152 hom., cov: 32)
• Consequence: CYB5RL NM_001031672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5RL	NM_001031672.4	c.541-237A>G		intron_variant		ENST00000534324.6
CYB5RL	NM_001353353.2	c.304-237A>G		intron_variant
CYB5RL	NM_001353354.2	c.97-237A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5RL	ENST00000534324.6	c.541-237A>G		intron_variant		5	NM_001031672.4	P1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100286 AN: 151978 Hom.: 34132 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.660 AC: 100348 AN: 152096 Hom.: 34152 Cov.: 32 AF XY: 0.659 AC XY: 48989 AN XY: 74352

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.671

Alfa AF: 0.712 Hom.: 19810

Bravo AF: 0.645

Asia WGS AF: 0.645 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.6
Dann	Benign	0.68

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: rs7520966; hg19: chr1-54645262;