Genetic Variant NM_001031672.4:c.913G>T (chr1-54174654-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.683

Publications

0 publications found

Variant links:

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]

CYB5RL links:

ENSG00000256407 (HGNC:):

ENSG00000256407 links:

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ACMG classification

Classification was made for transcript

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

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

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.:

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1460174

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

85776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111348

Other (OTH)

AF:

0.0000166

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0037

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.64

M_CAP

Benign

0.039

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.0031

MutationAssessor

Uncertain

2.0

PhyloP100

0.68

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

REVEL

Benign

0.27

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.018

Polyphen

0.72

Vest4

0.23

MutPred

0.50

Gain of glycosylation at A305 (P = 0.0401)

MVP

0.39

ClinPred

0.50

GERP RS

5.1

Varity_R

0.055

gMVP

0.38

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over