rs6502976

chr17-6764511-C-G

Variant summary

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

The NM_017523.5(XAF1):c.507+2271C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,030 control chromosomes in the GnomAD database, including 20,869 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 0.49 (20869 hom., cov: 32)
• Consequence: XAF1 NM_017523.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

Genes affected

XAF1 (HGNC:30932): (XIAP associated factor 1) This gene encodes a protein which binds to and counteracts the inhibitory effect of a member of the IAP (inhibitor of apoptosis) protein family. IAP proteins bind to and inhibit caspases which are activated during apoptosis. The proportion of IAPs and proteins which interfere with their activity, such as the encoded protein, affect the progress of the apoptosis signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XAF1	NM_017523.5	c.507+2271C>G		intron_variant		ENST00000361842.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XAF1	ENST00000361842.8	c.507+2271C>G		intron_variant		1	NM_017523.5	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74125 AN: 151912 Hom.: 20818 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.488 AC: 74220 AN: 152030 Hom.: 20869 Cov.: 32 AF XY: 0.488 AC XY: 36253 AN XY: 74296

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.473

Alfa AF: 0.428 Hom.: 2008

Bravo AF: 0.493

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.46

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: rs6502976; hg19: chr17-6667830;