rs16872759

Positions:

• chr4-22507935-T-A
• chr4-22507935-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA3	NM_145290.4	c.257+7593A>T		intron_variant		ENST00000334304.10	NP_660333.2
ADGRA3	XM_005248137.6	c.257+7593A>T		intron_variant			XP_005248194.1
ADGRA3	XR_007096381.1	n.539+7593A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA3	ENST00000334304.10	c.257+7593A>T		intron_variant		1	NM_145290.4	ENSP00000334952	P1
ADGRA3	ENST00000502482.1	c.257+7593A>T		intron_variant		1		ENSP00000421006
ADGRA3	ENST00000506346.1	n.169+7593A>T		intron_variant, non_coding_transcript_variant		3
ADGRA3	ENST00000513385.5	n.116+6530A>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.131

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.40

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: rs16872759; hg19: chr4-22509558;