rs4764971

Variant names:

• chr12-100238019-A-G
• rs4764971
• ENST00000553038.5:n.*542-3714A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The NM_001387205.1(DEPDC4):​c.1552T>C​(p.Ter518Glnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 969,742 control chromosomes in the GnomAD database, including 11,776 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 0.16 (2803 hom., cov: 31)
  • Exomes 𝑓: 0.14 (8973 hom.)
• Consequence: DEPDC4 NM_001387205.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

Genes affected

ACTR6 (HGNC:24025): (actin related protein 6) Predicted to enable nucleosome binding activity. Predicted to be involved in histone exchange. Predicted to be located in nucleus. Predicted to be part of Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC4 (HGNC:22952): (DEP domain containing 4) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in NM_001387205.1 Downstream stopcodon found after 518 codons.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC4	NM_001387205.1	c.1552T>C	p.Ter518Glnext*?	stop_lost	Exon 9 of 9		NP_001374134.1
DEPDC4	NM_001387206.1	c.1552T>C	p.Ter518Glnext*?	stop_lost	Exon 9 of 10		NP_001374135.1
DEPDC4	NM_001387210.1	c.1009T>C	p.Ter337Glnext*?	stop_lost	Exon 7 of 7		NP_001374139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR6	ENST00000553038.5	n.*542-3714A>G		intron_variant	Intron 9 of 9	1		ENSP00000447641.1
DEPDC4	ENST00000378244.6	n.*648T>C		non_coding_transcript_exon_variant	Exon 9 of 11	2		ENSP00000367490.2
DEPDC4	ENST00000549100.5	n.282T>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
DEPDC4	ENST00000378244.6	n.*648T>C		3_prime_UTR_variant	Exon 9 of 11	2		ENSP00000367490.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24296 AN: 151880 Hom.: 2803 Cov.: 31

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.139 AC: 114036 AN: 817744 Hom.: 8973 Cov.: 15 AF XY: 0.139 AC XY: 52737 AN XY: 378186

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.160 AC: 24298 AN: 151998 Hom.: 2803 Cov.: 31 AF XY: 0.173 AC XY: 12887 AN XY: 74290

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.163

Alfa AF: 0.152 Hom.: 4245

Bravo AF: 0.154

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4764971; hg19: chr12-100631797;