rs7970382

Positions:

• chr12-100210443-T-G

Variant summary

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

The NM_022496.5(ACTR6):​c.572+92T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,330,016 control chromosomes in the GnomAD database, including 40,316 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 0.32 (11615 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28701 hom.)
• Consequence: ACTR6 NM_022496.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR6	NM_022496.5	c.572+92T>G		intron_variant		ENST00000188312.7	NP_071941.1
ACTR6	NR_048568.2	n.750+92T>G		intron_variant, non_coding_transcript_variant
ACTR6	NR_048569.2	n.622+92T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR6	ENST00000188312.7	c.572+92T>G		intron_variant		1	NM_022496.5	ENSP00000188312	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49103 AN: 151770 Hom.: 11572 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.205 AC: 240929 AN: 1178130 Hom.: 28701 AF XY: 0.203 AC XY: 120915 AN XY: 595406

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.0560

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.324 AC: 49201 AN: 151886 Hom.: 11615 Cov.: 32 AF XY: 0.316 AC XY: 23469 AN XY: 74228

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0600

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.287

Alfa AF: 0.210 Hom.: 7681

Bravo AF: 0.344

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7970382; hg19: chr12-100604221; COSMIC: COSV51841847; COSMIC: COSV51841847;