rs1051858

chr14-58364424-A-Gchr14-58364424-A-T

Variant summary

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

The NM_002892.4(ARID4A):c.2335A>G(p.Thr779Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,612,356 control chromosomes in the GnomAD database, including 98,589 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.34 (9155 hom., cov: 32)
  • Exomes 𝑓: 0.35 (89434 hom.)
• Consequence: ARID4A NM_002892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

Genes affected

ARID4A (HGNC:9885): (AT-rich interaction domain 4A) The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.797327E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID4A	NM_002892.4	c.2335A>G	p.Thr779Ala	missense_variant	20/24	ENST00000355431.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID4A	ENST00000355431.8	c.2335A>G	p.Thr779Ala	missense_variant	20/24	1	NM_002892.4	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52205 AN: 151894 Hom.: 9140 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.343 AC: 85558 AN: 249570 Hom.: 15257 AF XY: 0.340 AC XY: 45966 AN XY: 135250

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.512

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.346 AC: 505394 AN: 1460344 Hom.: 89434 Cov.: 39 AF XY: 0.345 AC XY: 250337 AN XY: 726388

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.344 AC: 52258 AN: 152012 Hom.: 9155 Cov.: 32 AF XY: 0.345 AC XY: 25631 AN XY: 74316

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.320

Alfa AF: 0.330 Hom.: 20927

Bravo AF: 0.332

TwinsUK AF: 0.345 AC: 1279

ALSPAC AF: 0.345 AC: 1331

ESP6500AA AF: 0.342 AC: 1506

ESP6500EA AF: 0.330 AC: 2835

ExAC AF: 0.344 AC: 41785

Asia WGS AF: 0.411 AC: 1429 AN: 3474

EpiCase AF: 0.312

EpiControl AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	5.1
Dann	Benign	0.42
DEOGEN2	Benign	0.042	T;.;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.029	T;T;T;.;T
MetaRNN	Benign	0.000098	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.34	N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.35	N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.78	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.028
MPC		0.10
ClinPred		0.00030	T
GERP RS		1.5
Varity_R		0.027
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1051858; hg19: chr14-58831142; COSMIC: COSV62162398; COSMIC: COSV62162398;