rs1144122

Positions:

• chr3-100635680-A-G

Variant summary

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

The NM_032787.3(ADGRG7):​c.451A>G​(p.Lys151Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,822 control chromosomes in the GnomAD database, including 83,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5806 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77885 hom.)
• Consequence: ADGRG7 NM_032787.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015993416).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG7	NM_032787.3	c.451A>G	p.Lys151Glu	missense_variant	5/16	ENST00000273352.8
ADGRG7	XM_047449088.1	c.46A>G	p.Lys16Glu	missense_variant	3/14
ADGRG7	NM_001308362.1	c.-187A>G		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG7	ENST00000273352.8	c.451A>G	p.Lys151Glu	missense_variant	5/16	1	NM_032787.3	P1
ADGRG7	ENST00000475887.1	c.-187A>G		5_prime_UTR_variant	1/10	2
ADGRG7	ENST00000481361.1	n.143A>G		non_coding_transcript_exon_variant	1/4	4
ADGRG7	ENST00000493081.1	n.141A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39361 AN: 151856 Hom.: 5813 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.255 AC: 63484 AN: 248896 Hom.: 9651 AF XY: 0.260 AC XY: 34966 AN XY: 134412

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.0109

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.315 AC: 459497 AN: 1457848 Hom.: 77885 Cov.: 34 AF XY: 0.312 AC XY: 226350 AN XY: 725094

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.00794

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.259 AC: 39357 AN: 151974 Hom.: 5806 Cov.: 32 AF XY: 0.254 AC XY: 18835 AN XY: 74256

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.270

Alfa AF: 0.319 Hom.: 19063

Bravo AF: 0.251

TwinsUK AF: 0.369 AC: 1369

ALSPAC AF: 0.361 AC: 1392

ESP6500AA AF: 0.167 AC: 738

ESP6500EA AF: 0.343 AC: 2954

ExAC AF: 0.256 AC: 31050

Asia WGS AF: 0.0910 AC: 320 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0060
DANN	Benign	0.56
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.014
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.077
ClinPred		0.0017	T
GERP RS		-1.4
Varity_R		0.032
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1144122; hg19: chr3-100354524; COSMIC: COSV56295901;