NM_145290.4:c.257+7593A>T

Variant names:

• chr4-22507935-T-A
• rs16872759
• NM_145290.4:c.257+7593A>T

Variant summary

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

The NM_145290.4(ADGRA3):​c.257+7593A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,198 control chromosomes in the GnomAD database, including 1,557 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 0.13 (1557 hom., cov: 33)
• Consequence: ADGRA3 NM_145290.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 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.257+7593A>T		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.257+7593A>T		intron	N/A	ENSP00000334952.5
	ADGRA3	ENST00000502482.1	TSL:1	c.257+7593A>T		intron	N/A	ENSP00000421006.1
	ADGRA3	ENST00000506346.1	TSL:3	n.169+7593A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19800 AN: 152080 Hom.: 1554 Cov.: 33

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152198 Hom.: 1557 Cov.: 33 AF XY: 0.136 AC XY: 10136 AN XY: 74392

African (AFR) AF: 0.0781 AC: 3245 AN: 41546

American (AMR) AF: 0.151 AC: 2306 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1829 AN: 5166

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4824

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10586

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8688 AN: 68002

Other (OTH) AF: 0.131 AC: 277 AN: 2114

Alfa AF: 0.118 Hom.: 140

Bravo AF: 0.124

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.40
PhyloP100		-1.7
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: rs16872759; hg19: chr4-22509558;