1-54179589-T-C

Variant names:

• chr1-54179589-T-C
• rs7520966
• NM_001031672.4:c.541-237A>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.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
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5RL	NM_001031672.4	MANE Select	c.541-237A>G		intron	N/A	NP_001026842.2	Q6IPT4-1
	CYB5RL	NM_001353353.2		c.304-237A>G		intron	N/A	NP_001340282.1
	CYB5RL	NM_001353354.2		c.97-237A>G		intron	N/A	NP_001340283.1	Q6IPT4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5RL	ENST00000534324.6	TSL:5 MANE Select	c.541-237A>G		intron	N/A	ENSP00000434343.1	Q6IPT4-1
	CYB5RL	ENST00000420054.5	TSL:1	n.*535-237A>G		intron	N/A	ENSP00000403021.1	F8WDU4
	CYB5RL	ENST00000421415.5	TSL:1	n.*179-237A>G		intron	N/A	ENSP00000394709.1	F8VW03

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

African (AFR) AF: 0.478 AC: 19836 AN: 41472

American (AMR) AF: 0.670 AC: 10228 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2575 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3763 AN: 5166

South Asian (SAS) AF: 0.653 AC: 3145 AN: 4814

European-Finnish (FIN) AF: 0.771 AC: 8157 AN: 10582

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50417 AN: 68004

Other (OTH) AF: 0.671 AC: 1415 AN: 2108

Alfa AF: 0.709 Hom.: 27901

Bravo AF: 0.645

Asia WGS AF: 0.645 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

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: rs7520966; hg19: chr1-54645262;