Genetic Variant NM_052898.2:c.806+58471C>A (chr8-55161765-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052898.2(XKR4):c.806+58471C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 369,834 control chromosomes in the GnomAD database, including 16,482 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 0.32 ( 8577 hom., cov: 32)

Exomes 𝑓: 0.26 ( 7905 hom. )

Consequence

XKR4
NM_052898.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.632

Publications

1 publications found

Variant links:

Genes affected

XKR4 (HGNC:29394): (XK related 4) Enables phospholipid scramblase activity. Involved in phosphatidylserine exposure on apoptotic cell surface. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

XKR4 links:

ENSG00000253857 (HGNC:):

ENSG00000253857 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR4	NM_052898.2 link	c.806+58471C>A		intron_variant	Intron 1 of 2	ENST00000327381.7	NP_443130.1
LOC105375844	NR_188097.1 link	n.190+121C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
XKR4	ENST00000327381.7 link	c.806+58471C>A	intron_variant	Intron 1 of 2	1	NM_052898.2	ENSP00000328326.5
ENSG00000253857	ENST00000522559.2 link	n.206+121C>A	intron_variant	Intron 1 of 1	2
ENSG00000253857	ENST00000668329.2 link	n.217+121C>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48990

AN:

151970

Hom.:

8563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.262

AC:

57050

AN:

217746

Hom.:

7905

AF XY:

0.261

AC XY:

31713

AN XY:

121396

show subpopulations

African (AFR)

AF:

0.467

AC:

2609

AN:

5586

American (AMR)

AF:

0.224

AC:

3285

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1551

AN:

5196

East Asian (EAS)

AF:

0.273

AC:

2133

AN:

7802

South Asian (SAS)

AF:

0.245

AC:

11010

AN:

44966

European-Finnish (FIN)

AF:

0.251

AC:

2308

AN:

9180

Middle Eastern (MID)

AF:

0.349

AC:

537

AN:

1538

European-Non Finnish (NFE)

AF:

0.260

AC:

30767

AN:

118404

Other (OTH)

AF:

0.274

AC:

2850

AN:

10412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1954

3909

5863

7818

9772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.322

AC:

49032

AN:

152088

Hom.:

8577

Cov.:

AF XY:

0.323

AC XY:

24043

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.472

AC:

19568

AN:

41456

American (AMR)

AF:

0.271

AC:

4145

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1025

AN:

3468

East Asian (EAS)

AF:

0.277

AC:

1431

AN:

5166

South Asian (SAS)

AF:

0.238

AC:

1150

AN:

4822

European-Finnish (FIN)

AF:

0.269

AC:

2845

AN:

10578

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17839

AN:

67984

Other (OTH)

AF:

0.312

AC:

660

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1667

3334

5000

6667

8334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.200

Hom.:

628

Bravo

AF:

0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.69

(source)

DANN

Benign

0.74

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over