rs10504193

Variant names:

• chr8-55499614-T-C
• rs10504193
• NM_052898.2:c.1007-23667T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XKR4	NM_052898.2	c.1007-23667T>C		intron_variant	Intron 2 of 2	ENST00000327381.7	NP_443130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.1007-23667T>C		intron_variant	Intron 2 of 2	1	NM_052898.2	ENSP00000328326.5

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

African (AFR) AF: 0.0669 AC: 2780 AN: 41556

American (AMR) AF: 0.158 AC: 2418 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5160

South Asian (SAS) AF: 0.109 AC: 525 AN: 4826

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00635 AC: 432 AN: 68030

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

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
PhyloP100		-5.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10504193; hg19: chr8-56412173;