rs12542677

Positions:

• chr8-55255499-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_052898.2(XKR4):​c.807-102179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 152,140 control chromosomes in the GnomAD database, including 45 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 0.015 (45 hom., cov: 32)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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=-0.86).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0148 (2257/152140) while in subpopulation EAS AF= 0.0416 (215/5174). AF 95% confidence interval is 0.0377. There are 45 homozygotes in gnomad4. There are 1213 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR4	NM_052898.2	c.807-102179C>T		intron_variant		ENST00000327381.7	NP_443130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.807-102179C>T		intron_variant		1	NM_052898.2	ENSP00000328326	P1

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2254 AN: 152022 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0148 AC: 2257 AN: 152140 Hom.: 45 Cov.: 32 AF XY: 0.0163 AC XY: 1213 AN XY: 74394

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0416

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00500 Hom.: 23

Bravo AF: 0.0171

Asia WGS AF: 0.0210 AC: 74 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.80

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: rs12542677; hg19: chr8-56168059;