8-55161765-C-G

Position:

• chr8-55161765-C-G

Variant summary

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

The NM_052898.2(XKR4):​c.806+58471C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 370,244 control chromosomes in the GnomAD database, including 17 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 0.0065 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (2 hom.)
• Consequence: XKR4 NM_052898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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]

ENSG00000253857 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00652 (992/152128) while in subpopulation AFR AF= 0.0216 (896/41470). AF 95% confidence interval is 0.0204. There are 15 homozygotes in gnomad4. There are 489 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XKR4	NM_052898.2	c.806+58471C>G		intron_variant		ENST00000327381.7	NP_443130.1
LOC105375844	NR_188097.1	n.190+121C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XKR4	ENST00000327381.7	c.806+58471C>G		intron_variant		1	NM_052898.2	ENSP00000328326.5
ENSG00000253857	ENST00000522559.1	n.162+121C>G		intron_variant		2
ENSG00000253857	ENST00000668329.1	n.199+121C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152010 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000986 AC: 215 AN: 218116 Hom.: 2 AF XY: 0.000855 AC XY: 104 AN XY: 121574

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000666

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000590

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00652 AC: 992 AN: 152128 Hom.: 15 Cov.: 32 AF XY: 0.00657 AC XY: 489 AN XY: 74374

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.75

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: rs7837220; hg19: chr8-56074325;