5-93876252-T-C

Variant names:

• chr5-93876252-T-C
• rs10514378
• NM_032042.6:c.786+5218A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032042.6(ARB2A):​c.786+5218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,206 control chromosomes in the GnomAD database, including 62,532 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 0.90 (62532 hom., cov: 32)
• Consequence: ARB2A NM_032042.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 0 publications found

Genes affected

ARB2A (HGNC:25365): (ARB2 cotranscriptional regulator A) Predicted to contribute to siRNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA; neural crest cell development; and regulation of alternative mRNA splicing, via spliceosome. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032042.6. 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
	ARB2A	NM_032042.6	MANE Select	c.786+5218A>G		intron	N/A	NP_114431.2
	ARB2A	NM_001163417.1		c.648+5218A>G		intron	N/A	NP_001156889.1	Q8WUF8-3
	ARB2A	NM_001163418.1		c.456+5218A>G		intron	N/A	NP_001156890.1	Q8WUF8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARB2A	ENST00000395965.8	TSL:1 MANE Select	c.786+5218A>G		intron	N/A	ENSP00000379294.3	Q8WUF8-1
	ARB2A	ENST00000881906.1		c.786+5218A>G		intron	N/A	ENSP00000551965.1
	ARB2A	ENST00000881903.1		c.786+5218A>G		intron	N/A	ENSP00000551962.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137363 AN: 152088 Hom.: 62505 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.927

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

GnomAD4 genome AF: 0.903 AC: 137439 AN: 152206 Hom.: 62532 Cov.: 32 AF XY: 0.907 AC XY: 67509 AN XY: 74426

African (AFR) AF: 0.782 AC: 32476 AN: 41512

American (AMR) AF: 0.937 AC: 14335 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3219 AN: 3464

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5178

South Asian (SAS) AF: 0.977 AC: 4701 AN: 4810

European-Finnish (FIN) AF: 0.985 AC: 10459 AN: 10622

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64011 AN: 68000

Other (OTH) AF: 0.928 AC: 1962 AN: 2114

Alfa AF: 0.905 Hom.: 5172

Bravo AF: 0.893

Asia WGS AF: 0.975 AC: 3388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.86
PhyloP100		2.9
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: rs10514378; hg19: chr5-93211958;