Genetic Variant XKR4:c.1007-70263T>C (chr8-55453018-T-C) – 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.1007-70263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 641,924 control chromosomes in the GnomAD database, including 60,538 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 0.41 ( 13317 hom., cov: 32)

Exomes 𝑓: 0.43 ( 47221 hom. )

Consequence

XKR4
NM_052898.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.237

Publications

4 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:

SBF1P1 (HGNC:31098): (SET binding factor 1 pseudogene 1)

SBF1P1 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR4	NM_052898.2 link	c.1007-70263T>C		intron_variant	Intron 2 of 2	ENST00000327381.7	NP_443130.1	Q5GH76
SBF1P1	NR_027765.2 link	n.2304A>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7 link	c.1007-70263T>C		intron_variant	Intron 2 of 2	1	NM_052898.2	ENSP00000328326.5		Q5GH76
SBF1P1	ENST00000444527.2 link	n.2122A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61968

AN:

151892

Hom.:

13311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.416

GnomAD4 exome

AF:

0.435

AC:

213088

AN:

489914

Hom.:

47221

Cov.:

AF XY:

0.437

AC XY:

118508

AN XY:

271138

show subpopulations

African (AFR)

AF:

0.250

AC:

3642

AN:

14578

American (AMR)

AF:

0.494

AC:

19116

AN:

38698

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

5984

AN:

15820

East Asian (EAS)

AF:

0.485

AC:

10701

AN:

22082

South Asian (SAS)

AF:

0.460

AC:

30439

AN:

66198

European-Finnish (FIN)

AF:

0.497

AC:

18870

AN:

38002

Middle Eastern (MID)

AF:

0.427

AC:

1486

AN:

3484

European-Non Finnish (NFE)

AF:

0.422

AC:

112455

AN:

266404

Other (OTH)

AF:

0.422

AC:

10395

AN:

24648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

5911

11822

17732

23643

29554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.408

AC:

62013

AN:

152010

Hom.:

13317

Cov.:

AF XY:

0.413

AC XY:

30695

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.269

AC:

11181

AN:

41490

American (AMR)

AF:

0.459

AC:

7013

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1378

AN:

3468

East Asian (EAS)

AF:

0.534

AC:

2748

AN:

5146

South Asian (SAS)

AF:

0.464

AC:

2226

AN:

4802

European-Finnish (FIN)

AF:

0.524

AC:

5539

AN:

10572

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.452

AC:

30733

AN:

67940

Other (OTH)

AF:

0.415

AC:

876

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1882

3764

5646

7528

9410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.329

Hom.:

1075

Bravo

AF:

0.394

Asia WGS

AF:

0.529

AC:

1843

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

8.2

(source)

DANN

Benign

0.17

PhyloP100

-0.24

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over