rs1840882

Positions:

• chr8-70715487-C-T

Variant summary

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

The NM_001011720.2(XKR9):​c.493+8334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 152,074 control chromosomes in the GnomAD database, including 485 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 0.073 (485 hom., cov: 32)
• Consequence: XKR9 NM_001011720.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

Genes affected

XKR9 (HGNC:20937): (XK related 9) Predicted to enable phospholipid scramblase activity. Predicted to be involved in apoptotic process involved in development; engulfment of apoptotic cell; and 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XKR9	NM_001011720.2	c.493+8334C>T		intron_variant		ENST00000408926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XKR9	ENST00000408926.8	c.493+8334C>T		intron_variant		1	NM_001011720.2	P1
XKR9	ENST00000520030.5	c.493+8334C>T		intron_variant		1		P1
XKR9	ENST00000520092.5	c.*233+8334C>T		intron_variant, NMD_transcript_variant		2
XKR9	ENST00000520273.1	n.352+8334C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11051 AN: 151956 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0549

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.0844

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

GnomAD4 genome AF: 0.0727 AC: 11057 AN: 152074 Hom.: 485 Cov.: 32 AF XY: 0.0702 AC XY: 5219 AN XY: 74344

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.0548

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.0830

Alfa AF: 0.0898 Hom.: 620

Bravo AF: 0.0722

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.57

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: rs1840882; hg19: chr8-71627722;