1-235170778-C-T

Variant names:

• chr1-235170778-C-T
• rs6666401
• NM_016374.6:c.3811+1840G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016374.6(ARID4B):​c.3811+1840G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,060 control chromosomes in the GnomAD database, including 16,581 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 0.46 (16581 hom., cov: 28)
• Consequence: ARID4B NM_016374.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 2 publications found

Genes affected

ARID4B (HGNC:15550): (AT-rich interaction domain 4B) This gene encodes a protein with sequence similarity to retinoblastoma-binding protein-1. The encoded protein is a subunit of the histone deacetylase-dependant SIN3A transcriptional corepressor complex, which functions in diverse cellular processes including proliferation, differentiation, apoptosis, oncogenesis, and cell fate determination. The gene product is recognized by IgG antibody isolated from a breast cancer patient and appears to be a molecular marker associated with a broad range of human malignancies. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016374.6. 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
	ARID4B	NM_016374.6	MANE Select	c.3811+1840G>A		intron	N/A	NP_057458.4
	ARID4B	NM_001206794.2		c.3811+1840G>A		intron	N/A	NP_001193723.1	Q4LE39-1
	ARID4B	NM_031371.4		c.3553+1840G>A		intron	N/A	NP_112739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID4B	ENST00000264183.9	TSL:1 MANE Select	c.3811+1840G>A		intron	N/A	ENSP00000264183.3	Q4LE39-1
	ARID4B	ENST00000366603.6	TSL:1	c.3811+1840G>A		intron	N/A	ENSP00000355562.2	Q4LE39-1
	ARID4B	ENST00000349213.7	TSL:1	c.3553+1840G>A		intron	N/A	ENSP00000264184.4	Q4LE39-2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70061 AN: 150942 Hom.: 16560 Cov.: 28

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.464 AC: 70114 AN: 151060 Hom.: 16581 Cov.: 28 AF XY: 0.470 AC XY: 34646 AN XY: 73776

African (AFR) AF: 0.462 AC: 18982 AN: 41128

American (AMR) AF: 0.502 AC: 7630 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1543 AN: 3462

East Asian (EAS) AF: 0.249 AC: 1273 AN: 5122

South Asian (SAS) AF: 0.605 AC: 2891 AN: 4780

European-Finnish (FIN) AF: 0.501 AC: 5187 AN: 10348

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31275 AN: 67736

Other (OTH) AF: 0.439 AC: 921 AN: 2098

Alfa AF: 0.303 Hom.: 725

Bravo AF: 0.457

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-2.1
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: rs6666401; hg19: chr1-235334093;