rs2622542

Positions:

• chr8-55404181-C-G
• chr8-55404181-C-T

Variant summary

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

The NM_052898.2(XKR4):​c.1006+46304C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,020 control chromosomes in the GnomAD database, including 39,758 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 0.71 (39758 hom., cov: 32)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR4	NM_052898.2	c.1006+46304C>G		intron_variant		ENST00000327381.7	NP_443130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.1006+46304C>G		intron_variant		1	NM_052898.2	ENSP00000328326	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108288 AN: 151902 Hom.: 39711 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.713 AC: 108396 AN: 152020 Hom.: 39758 Cov.: 32 AF XY: 0.711 AC XY: 52781 AN XY: 74276

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.712

Alfa AF: 0.697 Hom.: 4672

Bravo AF: 0.718

Asia WGS AF: 0.631 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.9
DANN	Benign	0.32

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: rs2622542; hg19: chr8-56316741;