rs762288981

Variant names:

• chr1-54174654-C-A
• rs762288981
• NM_001031672.4:c.913G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-54174654-C-A
• chr1-54174654-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031672.4(CYB5RL):​c.913G>T​(p.Ala305Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,460,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CYB5RL NM_001031672.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.683
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1458297).

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.913G>T	p.Ala305Ser	missense	Exon 8 of 8	NP_001026842.2	Q6IPT4-1
	CYB5RL	NM_001353353.2		c.676G>T	p.Ala226Ser	missense	Exon 6 of 6	NP_001340282.1
	CYB5RL	NM_001353354.2		c.469G>T	p.Ala157Ser	missense	Exon 7 of 7	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.913G>T	p.Ala305Ser	missense	Exon 8 of 8	ENSP00000434343.1	Q6IPT4-1
	CYB5RL	ENST00000420054.5	TSL:1	n.*907G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000403021.1	F8WDU4
	CYB5RL	ENST00000421415.5	TSL:1	n.*551G>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000394709.1	F8VW03

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460174 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 726174

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111348

Other (OTH) AF: 0.0000166 AC: 1 AN: 60314

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.0031	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.68
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.018	D
Polyphen		0.72	P
Vest4		0.23
MutPred		0.50		Gain of glycosylation at A305 (P = 0.0401)
MVP		0.39
ClinPred		0.50	D
GERP RS		5.1
Varity_R		0.055
gMVP		0.38
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs762288981; hg19: chr1-54640327;