8-55453018-T-C

Position:

• chr8-55453018-T-C

Variant summary

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

The ENST00000327381.7(XKR4):​c.1007-70263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 641,924 control chromosomes in the GnomAD database, including 60,538 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 0.41 (13317 hom., cov: 32)
  • Exomes 𝑓: 0.43 (47221 hom.)
• Consequence: XKR4 ENST00000327381.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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]

SBF1P1 (HGNC:31098): (SET binding factor 1 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR4	NM_052898.2	c.1007-70263T>C		intron_variant		ENST00000327381.7	NP_443130.1
SBF1P1	NR_027765.2	n.2304A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.1007-70263T>C		intron_variant		1	NM_052898.2	ENSP00000328326	P1
SBF1P1	ENST00000444527.2	n.2122A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61968 AN: 151892 Hom.: 13311 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.435 AC: 213088 AN: 489914 Hom.: 47221 Cov.: 2 AF XY: 0.437 AC XY: 118508 AN XY: 271138

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.497

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.408 AC: 62013 AN: 152010 Hom.: 13317 Cov.: 32 AF XY: 0.413 AC XY: 30695 AN XY: 74280

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.415

Alfa AF: 0.333 Hom.: 1058

Bravo AF: 0.394

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.2
DANN	Benign	0.17

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: rs867531; hg19: chr8-56365578; COSMIC: COSV59298041;