4-22439843-G-T

Position:

• chr4-22439843-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA3	NM_145290.4	c.921-1423C>A		intron_variant		ENST00000334304.10	NP_660333.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA3	ENST00000334304.10	c.921-1423C>A		intron_variant		1	NM_145290.4	ENSP00000334952.5

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.803

Alfa AF: 0.856 Hom.: 66812

Bravo AF: 0.790

Asia WGS AF: 0.783 AC: 2715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1463000; hg19: chr4-22441466;