rs4957018

Variant names:

• chr5-313896-G-A
• rs4957018
• NM_013232.4:c.478-521G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286001 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	NM_013232.4	MANE Select	c.478-521G>A		intron	N/A	NP_037364.1	O75340-1
	PDCD6	NM_001267556.2		c.472-521G>A		intron	N/A	NP_001254485.1	O75340-2
	PDCD6	NM_001267557.2		c.274-521G>A		intron	N/A	NP_001254486.1	A0A087WZ38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	ENST00000264933.9	TSL:1 MANE Select	c.478-521G>A		intron	N/A	ENSP00000264933.4	O75340-1
	PDCD6	ENST00000507528.5	TSL:1	c.472-521G>A		intron	N/A	ENSP00000423815.1	O75340-2
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.208+9675G>A		intron	N/A	ENSP00000424601.2	A0A6Q8PH81

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

African (AFR) AF: 0.609 AC: 56 AN: 92

American (AMR) AF: 0.502 AC: 228 AN: 454

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 9 AN: 16

East Asian (EAS) AF: 0.100 AC: 7 AN: 70

South Asian (SAS) AF: 0.670 AC: 150 AN: 224

European-Finnish (FIN) AF: 0.682 AC: 15 AN: 22

Middle Eastern (MID) AF: 0.538 AC: 860 AN: 1598

European-Non Finnish (NFE) AF: 0.661 AC: 1174 AN: 1776

Other (OTH) AF: 0.568 AC: 159 AN: 280

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

African (AFR) AF: 0.717 AC: 29764 AN: 41498

American (AMR) AF: 0.577 AC: 8823 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1339 AN: 5156

South Asian (SAS) AF: 0.645 AC: 3114 AN: 4826

European-Finnish (FIN) AF: 0.668 AC: 7066 AN: 10572

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46368 AN: 67972

Other (OTH) AF: 0.648 AC: 1367 AN: 2110

Alfa AF: 0.675 Hom.: 17676

Bravo AF: 0.652

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4957018; hg19: chr5-314011; COSMIC: COSV53777864; COSMIC: COSV53777864;