14-58364424-A-G

Variant names:

• chr14-58364424-A-G
• rs1051858
• NM_002892.4:c.2335A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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]

TOMM20L-DT (HGNC:55443): (TOMM20L divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002892.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID4A	NM_002892.4	MANE Select	c.2335A>G	p.Thr779Ala	missense	Exon 20 of 24	NP_002883.3
	ARID4A	NM_023000.3		c.2335A>G	p.Thr779Ala	missense	Exon 20 of 24	NP_075376.2
	ARID4A	NM_023001.3		c.2335A>G	p.Thr779Ala	missense	Exon 20 of 23	NP_075377.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID4A	ENST00000355431.8	TSL:1 MANE Select	c.2335A>G	p.Thr779Ala	missense	Exon 20 of 24	ENSP00000347602.3
	ARID4A	ENST00000417477.2	TSL:1	c.1369A>G	p.Thr457Ala	missense	Exon 10 of 10	ENSP00000416053.2
	ARID4A	ENST00000941390.1		c.2395A>G	p.Thr799Ala	missense	Exon 20 of 24	ENSP00000611449.1

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

GnomAD2 exomes AF: 0.343 AC: 85558 AN: 249570 AF XY: 0.340

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 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

African (AFR) AF: 0.356 AC: 11883 AN: 33364

American (AMR) AF: 0.284 AC: 12655 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 6064 AN: 26108

East Asian (EAS) AF: 0.534 AC: 21128 AN: 39600

South Asian (SAS) AF: 0.302 AC: 25932 AN: 85744

European-Finnish (FIN) AF: 0.417 AC: 22236 AN: 53304

Middle Eastern (MID) AF: 0.266 AC: 1530 AN: 5754

European-Non Finnish (NFE) AF: 0.345 AC: 383775 AN: 1111556

Other (OTH) AF: 0.335 AC: 20191 AN: 60336

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

African (AFR) AF: 0.356 AC: 14759 AN: 41448

American (AMR) AF: 0.280 AC: 4281 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2628 AN: 5170

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4824

European-Finnish (FIN) AF: 0.414 AC: 4356 AN: 10512

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23066 AN: 67976

Other (OTH) AF: 0.320 AC: 677 AN: 2116

Alfa AF: 0.337 Hom.: 39079

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 v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.029	T
MetaRNN	Benign	0.000098	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.014
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.10
ClinPred		0.00030	T
GERP RS		1.5
Varity_R		0.027
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051858; hg19: chr14-58831142; COSMIC: COSV62162398; COSMIC: COSV62162398;