rs4957018

Positions:

• chr5-313896-G-A

Variant summary

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

The NM_013232.4(PDCD6):​c.478-521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 156,624 control chromosomes in the GnomAD database, including 34,706 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 0.66 (33899 hom., cov: 32)
  • Exomes 𝑓: 0.59 (807 hom.)
• Consequence: PDCD6 NM_013232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

Genes affected

PDCD6 (HGNC:8765): (programmed cell death 6) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

PDCD6-AHRR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD6	NM_013232.4	c.478-521G>A		intron_variant		ENST00000264933.9
PDCD6-AHRR	NR_165159.2	n.283+9675G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD6	ENST00000264933.9	c.478-521G>A		intron_variant		1	NM_013232.4	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100584 AN: 151974 Hom.: 33868 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.586 AC: 2658 AN: 4532 Hom.: 807 Cov.: 0 AF XY: 0.596 AC XY: 1365 AN XY: 2290

Gnomad4 AFR exome AF: 0.609

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.662 AC: 100677 AN: 152092 Hom.: 33899 Cov.: 32 AF XY: 0.659 AC XY: 48957 AN XY: 74334

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.648

Alfa AF: 0.675 Hom.: 15733

Bravo AF: 0.652

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4957018; hg19: chr5-314011; COSMIC: COSV53777864; COSMIC: COSV53777864;