rs374013482

Variant names:

• chr6-156779490-G-C
• rs374013482
• NM_001374828.1:c.1791+19G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-156779490-G-C
• chr6-156779490-G-A
• chr6-156779490-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001374828.1(ARID1B):​c.1791+19G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,339,434 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (13 hom.)
• Consequence: ARID1B NM_001374828.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

ARID1B (HGNC:18040): (AT-rich interaction domain 1B) This locus encodes an AT-rich DNA interacting domain-containing protein. The encoded protein is a component of the SWI/SNF chromatin remodeling complex and may play a role in cell-cycle activation. The protein encoded by this locus is similar to AT-rich interactive domain-containing protein 1A. These two proteins function as alternative, mutually exclusive ARID-subunits of the SWI/SNF complex. The associated complexes play opposing roles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ENSG00000296922 (HGNC:):

MIR4466 (HGNC:41726): (microRNA 4466) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-156779490-G-C is Benign according to our data. Variant chr6-156779490-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0024 (358/149450) while in subpopulation NFE AF = 0.0036 (241/66922). AF 95% confidence interval is 0.00323. There are 1 homozygotes in GnomAd4. There are 180 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 358 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374828.1. 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
	ARID1B	NM_001374828.1	MANE Select	c.1791+19G>C		intron	N/A	NP_001361757.1	A0A6Q8NVI4
	ARID1B	NM_001438482.1		c.1791+19G>C		intron	N/A	NP_001425411.1
	ARID1B	NM_001438483.1		c.1791+19G>C		intron	N/A	NP_001425412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID1B	ENST00000636930.2	TSL:2 MANE Select	c.1791+19G>C		intron	N/A	ENSP00000490491.2	A0A6Q8NVI4
	ARID1B	ENST00000346085.10	TSL:1	c.1791+19G>C		intron	N/A	ENSP00000344546.5	A0A3F2YNW7
	ARID1B	ENST00000350026.11	TSL:1	c.1791+19G>C		intron	N/A	ENSP00000055163.8	Q8NFD5-5

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 358 AN: 149340 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00716

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00251 AC: 243 AN: 96716 AF XY: 0.00259

Gnomad AFR exome AF: 0.000215

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00997

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00330 AC: 3925 AN: 1189984 Hom.: 13 Cov.: 33 AF XY: 0.00323 AC XY: 1895 AN XY: 587426

African (AFR) AF: 0.000421 AC: 10 AN: 23762

American (AMR) AF: 0.00124 AC: 22 AN: 17812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16648

East Asian (EAS) AF: 0.00 AC: 0 AN: 27040

South Asian (SAS) AF: 0.00195 AC: 103 AN: 52930

European-Finnish (FIN) AF: 0.00748 AC: 197 AN: 26352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4312

European-Non Finnish (NFE) AF: 0.00355 AC: 3466 AN: 975508

Other (OTH) AF: 0.00278 AC: 127 AN: 45620

GnomAD4 genome AF: 0.00240 AC: 358 AN: 149450 Hom.: 1 Cov.: 31 AF XY: 0.00247 AC XY: 180 AN XY: 72964

African (AFR) AF: 0.000412 AC: 17 AN: 41214

American (AMR) AF: 0.00186 AC: 28 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00716 AC: 69 AN: 9638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00360 AC: 241 AN: 66922

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00204

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Coffin-Siris syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.87
PhyloP100		1.5
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs374013482;

hg19: chr6-157100624;