8-11115326-T-C

Variant names:

• chr8-11115326-T-C
• rs10503414
• NM_173683.4:c.764+85250A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173683.4(XKR6):​c.764+85250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 152,356 control chromosomes in the GnomAD database, including 8 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 0.011 (8 hom., cov: 33)
• Consequence: XKR6 NM_173683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 2 publications found

Genes affected

XKR6 (HGNC:27806): (XK related 6) 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0108 (1648/152356) while in subpopulation SAS AF = 0.0253 (122/4822). AF 95% confidence interval is 0.0217. There are 8 homozygotes in GnomAd4. There are 767 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1648 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR6	NM_173683.4	c.764+85250A>G		intron_variant	Intron 1 of 2	ENST00000416569.3	NP_775954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR6	ENST00000416569.3	c.764+85250A>G		intron_variant	Intron 1 of 2	1	NM_173683.4	ENSP00000416707.2
XKR6	ENST00000529336.1	n.258-1234A>G		intron_variant	Intron 1 of 2	3		ENSP00000436594.1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1648 AN: 152238 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00883

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0108 AC: 1648 AN: 152356 Hom.: 8 Cov.: 33 AF XY: 0.0103 AC XY: 767 AN XY: 74504

African (AFR) AF: 0.00885 AC: 368 AN: 41584

American (AMR) AF: 0.00882 AC: 135 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4822

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 838 AN: 68034

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.0117 Hom.: 4

Bravo AF: 0.0106

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.83
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs10503414; hg19: chr8-10972836;