rs682705

Positions:

• chr1-54171744-G-A
• chr1-54171744-G-C

Variant summary

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

The NM_001031672.4(CYB5RL):​c.*2875C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 320,352 control chromosomes in the GnomAD database, including 76,768 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 (33903 hom., cov: 31)
  • Exomes 𝑓: 0.71 (42865 hom.)
• Consequence: CYB5RL NM_001031672.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5RL	NM_001031672.4	c.*2875C>T		3_prime_UTR_variant	8/8	ENST00000534324.6	NP_001026842.2
CYB5RL	NM_001353353.2	c.*2875C>T		3_prime_UTR_variant	6/6		NP_001340282.1
CYB5RL	NM_001353354.2	c.*2875C>T		3_prime_UTR_variant	7/7		NP_001340283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5RL	ENST00000534324	c.*2875C>T		3_prime_UTR_variant	8/8	5	NM_001031672.4	ENSP00000434343.1
ENSG00000256407	ENST00000637610.1	n.303+12417C>T		intron_variant		5		ENSP00000490901.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99845 AN: 151804 Hom.: 33884 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.709 AC: 119413 AN: 168430 Hom.: 42865 Cov.: 0 AF XY: 0.704 AC XY: 63517 AN XY: 90232

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.658 AC: 99906 AN: 151922 Hom.: 33903 Cov.: 31 AF XY: 0.657 AC XY: 48772 AN XY: 74244

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.669

Alfa AF: 0.685 Hom.: 5341

Bravo AF: 0.642

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	-0.83
CADD	Benign	3.1
DANN	Benign	0.69

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: rs682705; hg19: chr1-54637417;