1-54171494-T-C

Variant names:

• chr1-54171494-T-C
• rs625643
• NM_001031672.4:c.*3125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYB5RL	NM_001031672.4	c.*3125A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000534324.6	NP_001026842.2
CYB5RL	NM_001353353.2	c.*3125A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001340282.1
CYB5RL	NM_001353354.2	c.*3125A>G		3_prime_UTR_variant	Exon 7 of 7		NP_001340283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5RL	ENST00000534324.6	c.*3125A>G		3_prime_UTR_variant	Exon 8 of 8	5	NM_001031672.4	ENSP00000434343.1
ENSG00000256407	ENST00000637610.1	n.303+12667A>G		intron_variant	Intron 3 of 9	5		ENSP00000490901.1

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

GnomAD2 exomes AF: 0.743 AC: 94165 AN: 126782 AF XY: 0.734

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 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

African (AFR) AF: 0.625 AC: 5292 AN: 8462

American (AMR) AF: 0.819 AC: 22252 AN: 27166

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 7699 AN: 10534

East Asian (EAS) AF: 0.723 AC: 6552 AN: 9068

South Asian (SAS) AF: 0.666 AC: 39603 AN: 59508

European-Finnish (FIN) AF: 0.803 AC: 9940 AN: 12382

Middle Eastern (MID) AF: 0.698 AC: 1538 AN: 2204

European-Non Finnish (NFE) AF: 0.755 AC: 116610 AN: 154366

Other (OTH) AF: 0.737 AC: 10257 AN: 13908

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

African (AFR) AF: 0.634 AC: 26262 AN: 41414

American (AMR) AF: 0.766 AC: 11702 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2604 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3772 AN: 5150

South Asian (SAS) AF: 0.664 AC: 3189 AN: 4804

European-Finnish (FIN) AF: 0.807 AC: 8528 AN: 10568

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51373 AN: 67960

Other (OTH) AF: 0.726 AC: 1530 AN: 2106

Alfa AF: 0.744 Hom.: 106463

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
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs625643; hg19: chr1-54637167;