3-100655896-T-C

Position:

• chr3-100655896-T-C

Variant summary

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

The NM_032787.3(ADGRG7):​c.1727-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,515,678 control chromosomes in the GnomAD database, including 257,127 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (20578 hom., cov: 32)
  • Exomes 𝑓: 0.58 (236549 hom.)
• Consequence: ADGRG7 NM_032787.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003413
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

Genes affected

ADGRG7 (HGNC:19241): (adhesion G protein-coupled receptor G7) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRG7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG7	NM_032787.3	c.1727-3T>C		splice_region_variant, intron_variant		ENST00000273352.8	NP_116176.2
ADGRG7	NM_001308362.1	c.842-3T>C		splice_region_variant, intron_variant			NP_001295291.1
ADGRG7	XM_047449088.1	c.1322-3T>C		splice_region_variant, intron_variant			XP_047305044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.1727-3T>C		splice_region_variant, intron_variant		1	NM_032787.3	ENSP00000273352.3
ADGRG7	ENST00000475887.1	c.842-3T>C		splice_region_variant, intron_variant		2		ENSP00000419788.1
ADGRG7	ENST00000481506.1	n.987-3T>C		splice_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75539 AN: 151940 Hom.: 20568 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.510

GnomAD3 exomes AF: 0.573 AC: 143658 AN: 250562 Hom.: 42816 AF XY: 0.588 AC XY: 79605 AN XY: 135476

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.393

Gnomad SAS exome AF: 0.742

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.595

Gnomad OTH exome AF: 0.593

GnomAD4 exome AF: 0.583 AC: 794711 AN: 1363620 Hom.: 236549 Cov.: 20 AF XY: 0.589 AC XY: 402580 AN XY: 683404

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.497 AC: 75567 AN: 152058 Hom.: 20578 Cov.: 32 AF XY: 0.500 AC XY: 37192 AN XY: 74324

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.514

Alfa AF: 0.571 Hom.: 50285

Bravo AF: 0.475

Asia WGS AF: 0.599 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.6
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0080
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: rs9866111; hg19: chr3-100374740; COSMIC: COSV56294503;