rs2975997

Variant names:

• chr8-55438078-T-C
• rs2975997
• NM_052898.2:c.1006+80201T>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.1006+80201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,022 control chromosomes in the GnomAD database, including 40,739 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 0.72 (40739 hom., cov: 30)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR4	NM_052898.2	c.1006+80201T>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.1006+80201T>C		intron_variant	Intron 2 of 2	1	NM_052898.2	ENSP00000328326.5

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109693 AN: 151906 Hom.: 40683 Cov.: 30

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.722 AC: 109806 AN: 152022 Hom.: 40739 Cov.: 30 AF XY: 0.719 AC XY: 53417 AN XY: 74290

African (AFR) AF: 0.911 AC: 37810 AN: 41512

American (AMR) AF: 0.687 AC: 10500 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3080 AN: 5166

South Asian (SAS) AF: 0.626 AC: 3007 AN: 4800

European-Finnish (FIN) AF: 0.673 AC: 7102 AN: 10550

Middle Eastern (MID) AF: 0.628 AC: 182 AN: 290

European-Non Finnish (NFE) AF: 0.651 AC: 44249 AN: 67930

Other (OTH) AF: 0.696 AC: 1471 AN: 2112

Alfa AF: 0.669 Hom.: 146221

Bravo AF: 0.730

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.36
PhyloP100		-0.43
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: rs2975997; hg19: chr8-56350638;