14-72614360-A-G

Position:

• chr14-72614360-A-G

Variant summary

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

The NM_001280542.3(DPF3):​c.*4937T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,042 control chromosomes in the GnomAD database, including 33,394 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 0.65 (33394 hom., cov: 32)
• Consequence: DPF3 NM_001280542.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

Genes affected

DPF3 (HGNC:17427): (double PHD fingers 3) This gene encodes a member of the D4 protein family. The encoded protein is a transcription regulator that binds acetylated histones and is a component of the BAF chromatin remodeling complex. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPF3	NM_001280542.3	c.*4937T>C		3_prime_UTR_variant	11/11	ENST00000556509.6	NP_001267471.1
RGS6	XM_017021825.3	c.1423-15620A>G		intron_variant			XP_016877314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPF3	ENST00000556509.6	c.*4937T>C		3_prime_UTR_variant	11/11	1	NM_001280542.3	ENSP00000450518.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98836 AN: 151926 Hom.: 33340 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.651 AC: 98945 AN: 152042 Hom.: 33394 Cov.: 32 AF XY: 0.653 AC XY: 48546 AN XY: 74302

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.684

Alfa AF: 0.595 Hom.: 28960

Bravo AF: 0.665

Asia WGS AF: 0.855 AC: 2971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2526932; hg19: chr14-73081068;