rs4764971

Positions:

• chr12-100238019-A-G

Variant summary

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

The ENST00000553038.5(ACTR6):​c.*542-3714A>G variant causes a intron, NMD transcript 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: ACTR6 ENST00000553038.5 intron, NMD_transcript
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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/exons	MANE	UniProt
DEPDC4	NM_001387205.1	c.1552T>C	p.Ter518GlnextTer49	stop_lost	9/9
DEPDC4	NM_001387206.1	c.1552T>C	p.Ter518GlnextTer78	stop_lost	9/10
DEPDC4	NM_001387210.1	c.1009T>C	p.Ter337GlnextTer49	stop_lost	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR6	ENST00000553038.5	c.*542-3714A>G		intron_variant, NMD_transcript_variant		1
DEPDC4	ENST00000549100.5	n.282T>C		non_coding_transcript_exon_variant	3/3	3
DEPDC4	ENST00000378244.6	c.*648T>C		3_prime_UTR_variant, NMD_transcript_variant	9/11	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;