rs16872734

Positions:

• chr4-22483310-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145290.4(ADGRA3):​c.258-9467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 152,142 control chromosomes in the GnomAD database, including 321 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 0.061 (321 hom., cov: 33)
• Consequence: ADGRA3 NM_145290.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA3	NM_145290.4	c.258-9467C>T		intron_variant		ENST00000334304.10	NP_660333.2
ADGRA3	XM_047449703.1	c.-6021C>T		5_prime_UTR_variant	1/19		XP_047305659.1
ADGRA3	XM_005248137.6	c.258-9467C>T		intron_variant			XP_005248194.1
ADGRA3	XR_007096381.1	n.540-9467C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA3	ENST00000334304.10	c.258-9467C>T		intron_variant		1	NM_145290.4	ENSP00000334952	P1
ADGRA3	ENST00000502482.1	c.258-9467C>T		intron_variant		1		ENSP00000421006
ADGRA3	ENST00000506346.1	n.170-9467C>T		intron_variant, non_coding_transcript_variant		3
ADGRA3	ENST00000513385.5	n.117-9467C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9337 AN: 152024 Hom.: 321 Cov.: 33

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0614 AC: 9342 AN: 152142 Hom.: 321 Cov.: 33 AF XY: 0.0608 AC XY: 4520 AN XY: 74368

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0316

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0536 Hom.: 225

Bravo AF: 0.0631

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.44

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: rs16872734; hg19: chr4-22484933;