rs4240671

Variant names:

• chr8-10910238-G-A
• rs4240671
• NM_173683.4:c.962-11322C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173683.4(XKR6):​c.962-11322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,872 control chromosomes in the GnomAD database, including 18,810 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 0.48 (18810 hom., cov: 31)
• Consequence: XKR6 NM_173683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 21 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XKR6	NM_173683.4	c.962-11322C>T		intron_variant	Intron 2 of 2	ENST00000416569.3	NP_775954.2
XKR6	XM_024447129.2	c.962-11223C>T		intron_variant	Intron 2 of 2		XP_024302897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XKR6	ENST00000416569.3	c.962-11322C>T		intron_variant	Intron 2 of 2	1	NM_173683.4	ENSP00000416707.2
XKR6	ENST00000382461.8	c.185-11322C>T		intron_variant	Intron 2 of 2	1		ENSP00000371900.4

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72888 AN: 151754 Hom.: 18788 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.480 AC: 72945 AN: 151872 Hom.: 18810 Cov.: 31 AF XY: 0.468 AC XY: 34761 AN XY: 74224

African (AFR) AF: 0.618 AC: 25561 AN: 41374

American (AMR) AF: 0.347 AC: 5297 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.0217 AC: 112 AN: 5172

South Asian (SAS) AF: 0.404 AC: 1932 AN: 4788

European-Finnish (FIN) AF: 0.353 AC: 3719 AN: 10524

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32948 AN: 67970

Other (OTH) AF: 0.460 AC: 968 AN: 2106

Alfa AF: 0.483 Hom.: 78683

Bravo AF: 0.479

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.67
PhyloP100		-0.85
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: rs4240671; hg19: chr8-10767748;