dbSNP rs754778102: VKORC1L1:p.Cys58Cys (chr7-65873545-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_173517.6(VKORC1L1):c.174C>T(p.Cys58Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,562,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

VKORC1L1
NM_173517.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

Publications

0 publications found

Variant links:

Genes affected

VKORC1L1 (HGNC:21492): (vitamin K epoxide reductase complex subunit 1 like 1) This gene encodes an enzyme important in the vitamin K cycle, which is involved in the carboxylation of glutamate residues present in vitamin K-dependent proteins. The encoded enzyme catalyzes the de-epoxidation of vitamin K 2,3-epoxide. Oxidative stress may upregulate expression of this gene and the encoded protein may protect cells and membrane proteins form oxidative damage. This gene and a related gene (Gene ID: 79001) may have arisen by gene duplication of an ancestral gene. [provided by RefSeq, Oct 2016]

VKORC1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-65873545-C-T is Benign according to our data. Variant chr7-65873545-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657524.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173517.6. 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
	VKORC1L1	NM_173517.6	MANE Select	c.174C>T	p.Cys58Cys	synonymous	Exon 1 of 3	NP_775788.2
	VKORC1L1	NM_001284342.3		c.174C>T	p.Cys58Cys	synonymous	Exon 1 of 2	NP_001271271.1	Q8N0U8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VKORC1L1	ENST00000360768.5	TSL:1 MANE Select	c.174C>T	p.Cys58Cys	synonymous	Exon 1 of 3	ENSP00000353998.2	Q8N0U8-1
VKORC1L1	ENST00000880558.1		c.174C>T	p.Cys58Cys	synonymous	Exon 1 of 4	ENSP00000550617.1
VKORC1L1	ENST00000648187.1		c.315C>T	p.Cys105Cys	synonymous	Exon 1 of 3	ENSP00000497458.1	A0A3B3ISV4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000217

AC:

AN:

184572

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000483

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1411524

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

701190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31018

American (AMR)

AF:

0.00

AC:

AN:

38688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24812

East Asian (EAS)

AF:

0.00

AC:

AN:

36374

South Asian (SAS)

AF:

0.00

AC:

AN:

82004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

0.0000330

AC:

AN:

1090390

Other (OTH)

AF:

0.0000172

AC:

AN:

58110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

AF:

0.0000132

AC:

AN:

151024

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41344

American (AMR)

AF:

0.00

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67602

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.3

PromoterAI

0.041

Neutral

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over