Variant 1-54174818-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031672.4(CYB5RL):c.749G>T(p.Ser250Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 ( 0 hom. )

Consequence

CYB5RL
NM_001031672.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.956

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05831027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5RL	NM_001031672.4 link	c.749G>T	p.Ser250Ile	missense_variant	8/8	ENST00000534324.6	NP_001026842.2	Q6IPT4-1
CYB5RL	NM_001353353.2 link	c.512G>T	p.Ser171Ile	missense_variant	6/6		NP_001340282.1
CYB5RL	NM_001353354.2 link	c.305G>T	p.Ser102Ile	missense_variant	7/7		NP_001340283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5RL	ENST00000534324.6 link	c.749G>T	p.Ser250Ile	missense_variant	8/8	5	NM_001031672.4	ENSP00000434343.1		Q6IPT4-1
ENSG00000256407	ENST00000637610.1 link	n.303+9343G>T		intron_variant		5		ENSP00000490901.1		A0A1B0GWF0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460304

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726464

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.749G>T (p.S250I) alteration is located in exon 8 (coding exon 6) of the CYB5RL gene. This alteration results from a G to T substitution at nucleotide position 749, causing the serine (S) at amino acid position 250 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.3

DANN

Benign

0.90

DEOGEN2

Benign

0.096

.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.56

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.97

.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.19

Sift

Benign

0.15

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.061

.;B

Vest4

0.19

MutPred

0.47

.;Loss of disorder (P = 0.0024);

MVP

0.24

ClinPred

0.10

GERP RS

-1.7

Varity_R

0.081

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over