rs1144122

Variant names:

• chr3-100635680-A-G
• rs1144122
• NM_032787.3:c.451A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K151R) has been classified as Uncertain significance.

• 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
• Publications: 28 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 (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 rank	MANE	Protein	UniProt
ADGRG7	NM_032787.3	c.451A>G	p.Lys151Glu	missense_variant	Exon 5 of 16	ENST00000273352.8	NP_116176.2
ADGRG7	XM_047449088.1	c.46A>G	p.Lys16Glu	missense_variant	Exon 3 of 14		XP_047305044.1
ADGRG7	NM_001308362.1	c.-187A>G		5_prime_UTR_variant	Exon 1 of 10		NP_001295291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG7	ENST00000273352.8	c.451A>G	p.Lys151Glu	missense_variant	Exon 5 of 16	1	NM_032787.3	ENSP00000273352.3
ADGRG7	ENST00000481361.1	n.143A>G		non_coding_transcript_exon_variant	Exon 1 of 4	4
ADGRG7	ENST00000493081.1	n.141A>G		non_coding_transcript_exon_variant	Exon 1 of 2	4
ADGRG7	ENST00000475887.1	c.-187A>G		5_prime_UTR_variant	Exon 1 of 10	2		ENSP00000419788.1

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

GnomAD2 exomes AF: 0.255 AC: 63484 AN: 248896 AF XY: 0.260

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 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

African (AFR) AF: 0.154 AC: 5144 AN: 33360

American (AMR) AF: 0.160 AC: 7082 AN: 44240

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9754 AN: 26036

East Asian (EAS) AF: 0.00794 AC: 315 AN: 39664

South Asian (SAS) AF: 0.163 AC: 13949 AN: 85394

European-Finnish (FIN) AF: 0.301 AC: 16065 AN: 53344

Middle Eastern (MID) AF: 0.286 AC: 1648 AN: 5758

European-Non Finnish (NFE) AF: 0.349 AC: 387357 AN: 1109810

Other (OTH) AF: 0.302 AC: 18183 AN: 60242

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

African (AFR) AF: 0.161 AC: 6693 AN: 41476

American (AMR) AF: 0.213 AC: 3260 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5180

South Asian (SAS) AF: 0.148 AC: 713 AN: 4804

European-Finnish (FIN) AF: 0.297 AC: 3138 AN: 10550

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23164 AN: 67914

Other (OTH) AF: 0.270 AC: 571 AN: 2112

Alfa AF: 0.308 Hom.: 25517

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
PhyloP100		-2.0
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
PromoterAI		-0.0017	Neutral
Varity_R		0.032
gMVP		0.27
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1144122; hg19: chr3-100354524; COSMIC: COSV56295901;