NM_032042.6:c.786+5218A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032042.6(ARB2A):​c.786+5218A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).

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>C		intron	N/A	NP_114431.2
	ARB2A	NM_001163417.1		c.648+5218A>C		intron	N/A	NP_001156889.1	Q8WUF8-3
	ARB2A	NM_001163418.1		c.456+5218A>C		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>C		intron	N/A	ENSP00000379294.3	Q8WUF8-1
	ARB2A	ENST00000881906.1		c.786+5218A>C		intron	N/A	ENSP00000551965.1
	ARB2A	ENST00000881903.1		c.786+5218A>C		intron	N/A	ENSP00000551962.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74300

African (AFR) AF: 0.0000483 AC: 2 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 5172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.84
PhyloP100		2.9

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;