rs2230098

Variant names:

• chr14-58364260-A-G
• rs2230098
• NM_002892.4:c.2171A>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.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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 15 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=0.0014016628).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0579 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.2171A>G	p.Asn724Ser	missense	Exon 20 of 24	NP_002883.3
	ARID4A	NM_023000.3		c.2171A>G	p.Asn724Ser	missense	Exon 20 of 24	NP_075376.2	P29374-2
	ARID4A	NM_023001.3		c.2171A>G	p.Asn724Ser	missense	Exon 20 of 23	NP_075377.2	P29374-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID4A	ENST00000355431.8	TSL:1 MANE Select	c.2171A>G	p.Asn724Ser	missense	Exon 20 of 24	ENSP00000347602.3	P29374-1
	ARID4A	ENST00000417477.2	TSL:1	c.1205A>G	p.Asn402Ser	missense	Exon 10 of 10	ENSP00000416053.2	H7C485
	ARID4A	ENST00000941390.1		c.2231A>G	p.Asn744Ser	missense	Exon 20 of 24	ENSP00000611449.1

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

GnomAD2 exomes AF: 0.0407 AC: 7980 AN: 195854 AF XY: 0.0405

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 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

African (AFR) AF: 0.0121 AC: 358 AN: 29698

American (AMR) AF: 0.0198 AC: 520 AN: 26274

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 298 AN: 23000

East Asian (EAS) AF: 0.0000792 AC: 3 AN: 37888

South Asian (SAS) AF: 0.0132 AC: 969 AN: 73318

European-Finnish (FIN) AF: 0.0650 AC: 3337 AN: 51356

Middle Eastern (MID) AF: 0.0169 AC: 92 AN: 5444

European-Non Finnish (NFE) AF: 0.0625 AC: 67921 AN: 1086358

Other (OTH) AF: 0.0456 AC: 2598 AN: 56942

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

African (AFR) AF: 0.0144 AC: 598 AN: 41560

American (AMR) AF: 0.0226 AC: 346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4826

European-Finnish (FIN) AF: 0.0641 AC: 677 AN: 10558

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0594 AC: 4038 AN: 67992

Other (OTH) AF: 0.0384 AC: 81 AN: 2112

Alfa AF: 0.0483 Hom.: 493

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 v4.9

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
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.42	N
PhyloP100		-0.028
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.064
Sift	Benign	0.34	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.12
MPC		0.085
ClinPred		0.0093	T
GERP RS		-3.3
Varity_R		0.016
gMVP		0.052
Mutation Taster		=99/1	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: rs2230098; hg19: chr14-58830978; COSMIC: COSV62165573; COSMIC: COSV62165573;