rs3840452

Variant names:

• chr1-235327076-CA-C
• rs3840452
• NM_016374.6:c.-49-109delT

Your query was ambiguous. Multiple possible variants found:

• chr1-235327076-CA-C
• chr1-235327076-CA-CAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016374.6(ARID4B):​c.-49-109delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15802 hom., cov: 0)
  • Exomes 𝑓: 0.46 (64376 hom.)
• Consequence: ARID4B NM_016374.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 5 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]

GGPS1 (HGNC:4249): (geranylgeranyl diphosphate synthase 1) This gene is a member of the prenyltransferase family and encodes a protein with geranylgeranyl diphosphate (GGPP) synthase activity. The enzyme catalyzes the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. GGPP is an important molecule responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor. Alternate transcriptional splice variants, both protein-coding and non-protein-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

GGPS1 Gene-Disease associations (from GenCC):

• muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID4B	NM_016374.6	c.-49-109delT		intron_variant	Intron 1 of 23	ENST00000264183.9	NP_057458.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID4B	ENST00000264183.9	c.-49-109delT		intron_variant	Intron 1 of 23	1	NM_016374.6	ENSP00000264183.3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68613 AN: 151806 Hom.: 15782 Cov.: 0

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.460 AC: 271873 AN: 591008 Hom.: 64376 Cov.: 0 AF XY: 0.468 AC XY: 146220 AN XY: 312504

African (AFR) AF: 0.446 AC: 6595 AN: 14776

American (AMR) AF: 0.431 AC: 9439 AN: 21898

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 6756 AN: 15602

East Asian (EAS) AF: 0.273 AC: 8790 AN: 32198

South Asian (SAS) AF: 0.593 AC: 32738 AN: 55220

European-Finnish (FIN) AF: 0.476 AC: 20617 AN: 43296

Middle Eastern (MID) AF: 0.467 AC: 1049 AN: 2246

European-Non Finnish (NFE) AF: 0.459 AC: 172411 AN: 375620

Other (OTH) AF: 0.447 AC: 13478 AN: 30152

GnomAD4 genome AF: 0.452 AC: 68668 AN: 151924 Hom.: 15802 Cov.: 0 AF XY: 0.456 AC XY: 33832 AN XY: 74234

African (AFR) AF: 0.456 AC: 18883 AN: 41432

American (AMR) AF: 0.428 AC: 6543 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1276 AN: 5168

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4820

European-Finnish (FIN) AF: 0.477 AC: 5027 AN: 10538

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31252 AN: 67904

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.451 Hom.: 1886

Bravo AF: 0.441

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3840452; hg19: chr1-235490391; COSMIC: COSV107255034; COSMIC: COSV107255034;