Genetic Variant NM_052898.2: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

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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