4-22439843-G-T

Variant names:

• chr4-22439843-G-T
• rs1463000
• NM_145290.4:c.921-1423C>A

Variant summary

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

The NM_145290.4(ADGRA3):​c.921-1423C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,046 control chromosomes in the GnomAD database, including 49,090 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 0.80 (49090 hom., cov: 32)
• Consequence: ADGRA3 NM_145290.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 1 publications found

Genes affected

ADGRA3 (HGNC:13839): (adhesion G protein-coupled receptor A3) This gene encodes a member of the G protein-coupled receptor superfamily. This membrane protein may play a role in tumor angiogenesis through its interaction with the human homolog of the Drosophila disc large tumor suppressor gene. This gene is mapped to a candidate region of chromosome 4 which may be associated with bipolar disorder and schizophrenia. [provided by RefSeq, Oct 2012]

ADGRA3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145290.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA3	NM_145290.4	MANE Select	c.921-1423C>A		intron	N/A	NP_660333.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA3	ENST00000334304.10	TSL:1 MANE Select	c.921-1423C>A		intron	N/A	ENSP00000334952.5
	ADGRA3	ENST00000502482.1	TSL:1	c.921-1423C>A		intron	N/A	ENSP00000421006.1
	ADGRA3	ENST00000508133.5	TSL:1	c.243-1423C>A		intron	N/A	ENSP00000422606.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121042 AN: 151930 Hom.: 49080 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.796 AC: 121101 AN: 152046 Hom.: 49090 Cov.: 32 AF XY: 0.797 AC XY: 59217 AN XY: 74326

African (AFR) AF: 0.630 AC: 26100 AN: 41436

American (AMR) AF: 0.826 AC: 12616 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3045 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4330 AN: 5164

South Asian (SAS) AF: 0.831 AC: 3997 AN: 4812

European-Finnish (FIN) AF: 0.855 AC: 9052 AN: 10588

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59187 AN: 67988

Other (OTH) AF: 0.803 AC: 1692 AN: 2106

Alfa AF: 0.839 Hom.: 88794

Bravo AF: 0.790

Asia WGS AF: 0.783 AC: 2715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.15
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: rs1463000; hg19: chr4-22441466;