chr1-54171494-T-C

Position:

• chr1-54171494-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.*3125A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 449,544 control chromosomes in the GnomAD database, including 121,626 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 0.72 (39936 hom., cov: 30)
  • Exomes 𝑓: 0.74 (81690 hom.)
• Consequence: CYB5RL NM_001031672.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB5RL	NM_001031672.4	c.*3125A>G		3_prime_UTR_variant	8/8	ENST00000534324.6
CYB5RL	NM_001353353.2	c.*3125A>G		3_prime_UTR_variant	6/6
CYB5RL	NM_001353354.2	c.*3125A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYB5RL	ENST00000534324.6	c.*3125A>G		3_prime_UTR_variant	8/8	5	NM_001031672.4	P1
CYB5RL	ENST00000287899.13	c.*3125A>G		3_prime_UTR_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109685 AN: 151828 Hom.: 39897 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.726

GnomAD3 exomes AF: 0.743 AC: 94165 AN: 126782 Hom.: 35196 AF XY: 0.734 AC XY: 50853 AN XY: 69292

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.818

Gnomad ASJ exome AF: 0.732

Gnomad EAS exome AF: 0.734

Gnomad SAS exome AF: 0.668

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.738 AC: 219743 AN: 297598 Hom.: 81690 Cov.: 0 AF XY: 0.731 AC XY: 123344 AN XY: 168770

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.803

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.737

GnomAD4 genome AF: 0.722 AC: 109780 AN: 151946 Hom.: 39936 Cov.: 30 AF XY: 0.722 AC XY: 53644 AN XY: 74274

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.726

Alfa AF: 0.746 Hom.: 73839

Bravo AF: 0.717

Asia WGS AF: 0.671 AC: 2334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.39

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: rs625643; hg19: chr1-54637167;