rs10504193

chr8-55499614-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052898.2(XKR4):c.1007-23667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,270 control chromosomes in the GnomAD database, including 605 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 0.053 (605 hom., cov: 32)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.49

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR4	NM_052898.2	c.1007-23667T>C		intron_variant		ENST00000327381.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR4	ENST00000327381.7	c.1007-23667T>C		intron_variant		1	NM_052898.2	P1

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7981 AN: 152150 Hom.: 602 Cov.: 32

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00633

Gnomad OTH AF: 0.0602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0526 AC: 8010 AN: 152270 Hom.: 605 Cov.: 32 AF XY: 0.0566 AC XY: 4212 AN XY: 74450

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0495 Hom.: 105

Bravo AF: 0.0654

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.010
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs10504193; hg19: chr8-56412173;