Genetic Variant XKR4:c.806+58471C>G (chr8-55161765-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_052898.2(XKR4):c.806+58471C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 370,244 control chromosomes in the GnomAD database, including 17 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 0.0065 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 2 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:

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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).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00652 (992/152128) while in subpopulation AFR AF = 0.0216 (896/41470). AF 95% confidence interval is 0.0204. There are 15 homozygotes in GnomAd4. There are 489 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

987

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

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:

0.000235

Gnomad OTH

AF:

0.00430

GnomAD4 exome

AF:

0.000986

AC:

215

AN:

218116

Hom.:

AF XY:

0.000855

AC XY:

104

AN XY:

121574

show subpopulations

African (AFR)

AF:

0.0243

AC:

136

AN:

5602

American (AMR)

AF:

0.00320

AC:

AN:

14692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5210

East Asian (EAS)

AF:

0.00

AC:

AN:

7824

South Asian (SAS)

AF:

0.0000666

AC:

AN:

45018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9206

Middle Eastern (MID)

AF:

0.00130

AC:

AN:

1542

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

118590

Other (OTH)

AF:

0.00192

AC:

AN:

10432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00652

AC:

992

AN:

152128

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

489

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0216

AC:

896

AN:

41470

American (AMR)

AF:

0.00458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67996

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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.:

628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.47

(source)

DANN

Benign

0.75

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism

(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