3-100655896-T-C

Variant names:

• chr3-100655896-T-C
• rs9866111
• NM_032787.3:c.1727-3T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADGRG7	NM_032787.3	c.1727-3T>C		splice_region_variant, intron_variant	Intron 12 of 15	ENST00000273352.8	NP_116176.2
ADGRG7	NM_001308362.1	c.842-3T>C		splice_region_variant, intron_variant	Intron 6 of 9		NP_001295291.1
ADGRG7	XM_047449088.1	c.1322-3T>C		splice_region_variant, intron_variant	Intron 10 of 13		XP_047305044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.1727-3T>C		splice_region_variant, intron_variant	Intron 12 of 15	1	NM_032787.3	ENSP00000273352.3
ADGRG7	ENST00000475887.1	c.842-3T>C		splice_region_variant, intron_variant	Intron 6 of 9	2		ENSP00000419788.1
ADGRG7	ENST00000481506.1	n.987-3T>C		splice_region_variant, intron_variant	Intron 1 of 4	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

GnomAD2 exomes AF: 0.573 AC: 143658 AN: 250562 AF XY: 0.588

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 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

African (AFR) AF: 0.239 AC: 7642 AN: 31970

American (AMR) AF: 0.583 AC: 25940 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14503 AN: 25346

East Asian (EAS) AF: 0.410 AC: 16040 AN: 39166

South Asian (SAS) AF: 0.739 AC: 61557 AN: 83264

European-Finnish (FIN) AF: 0.592 AC: 31455 AN: 53110

Middle Eastern (MID) AF: 0.576 AC: 3214 AN: 5584

European-Non Finnish (NFE) AF: 0.588 AC: 602339 AN: 1023814

Other (OTH) AF: 0.563 AC: 32021 AN: 56906

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

African (AFR) AF: 0.260 AC: 10793 AN: 41472

American (AMR) AF: 0.555 AC: 8478 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1907 AN: 3464

East Asian (EAS) AF: 0.400 AC: 2068 AN: 5166

South Asian (SAS) AF: 0.744 AC: 3589 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6239 AN: 10564

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40673 AN: 67962

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.555 Hom.: 73475

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
PhyloP100		-0.33
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9866111; hg19: chr3-100374740; COSMIC: COSV56294503;