rs2230098

Positions:

• chr14-58364260-A-G

Variant summary

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

The NM_002892.4(ARID4A):​c.2171A>G​(p.Asn724Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 1,542,474 control chromosomes in the GnomAD database, including 2,589 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 0.038 (160 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2429 hom.)
• Consequence: ARID4A NM_002892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=0.0014016628).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID4A	NM_002892.4	c.2171A>G	p.Asn724Ser	missense_variant	20/24	ENST00000355431.8	NP_002883.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID4A	ENST00000355431.8	c.2171A>G	p.Asn724Ser	missense_variant	20/24	1	NM_002892.4	ENSP00000347602.3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5855 AN: 152078 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0388

GnomAD3 exomes AF: 0.0407 AC: 7980 AN: 195854 Hom.: 223 AF XY: 0.0405 AC XY: 4395 AN XY: 108426

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0161

Gnomad EAS exome AF: 0.0000693

Gnomad SAS exome AF: 0.0128

Gnomad FIN exome AF: 0.0636

Gnomad NFE exome AF: 0.0579

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0547 AC: 76096 AN: 1390278 Hom.: 2429 Cov.: 30 AF XY: 0.0537 AC XY: 37061 AN XY: 690552

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.0000792

Gnomad4 SAS exome AF: 0.0132

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.0456

GnomAD4 genome AF: 0.0385 AC: 5852 AN: 152196 Hom.: 160 Cov.: 32 AF XY: 0.0370 AC XY: 2756 AN XY: 74452

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0641

Gnomad4 NFE AF: 0.0594

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0501 Hom.: 441

Bravo AF: 0.0342

TwinsUK AF: 0.0591 AC: 219

ALSPAC AF: 0.0605 AC: 233

ESP6500AA AF: 0.0156 AC: 63

ESP6500EA AF: 0.0452 AC: 380

ExAC AF: 0.0388 AC: 4688

Asia WGS AF: 0.00723 AC: 26 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.31
DEOGEN2	Benign	0.039	T;.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.80	T;T;T;.;T
MetaRNN	Benign	0.0014	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.42	N;N;N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.20	N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.34	T;T;T;T;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.0010	B;B;B;B;.
Vest4		0.12
MPC		0.085
ClinPred		0.0093	T
GERP RS		-3.3
Varity_R		0.016
gMVP		0.052

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: rs2230098; hg19: chr14-58830978; COSMIC: COSV62165573; COSMIC: COSV62165573;