NM_001304376.3:c.846C>T

Variant names:

• chr16-57567880-C-T
• rs9937918
• NM_001304376.3:c.846C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001304376.3(ADGRG5):​c.846C>T​(p.Arg282Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,610,494 control chromosomes in the GnomAD database, including 86,127 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 0.34 (9556 hom., cov: 32)
  • Exomes 𝑓: 0.31 (76571 hom.)
• Consequence: ADGRG5 NM_001304376.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27
• Publications: 24 publications found

Genes affected

ADGRG5 (HGNC:19010): (adhesion G protein-coupled receptor G5) This gene encodes a member of the adhesion family of G-protein coupled receptors. Members of this family are characterized by long N-termini and multiple functional domains. They may play a role in the immune system as well as in the central nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

LOC105371291 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304376.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG5	NM_001304376.3	MANE Select	c.846C>T	p.Arg282Arg	synonymous	Exon 9 of 12	NP_001291305.1
	ADGRG5	NM_153837.4		c.846C>T	p.Arg282Arg	synonymous	Exon 9 of 12	NP_722579.1
	ADGRG5	NM_001318481.2		c.846C>T	p.Arg282Arg	synonymous	Exon 9 of 11	NP_001305410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG5	ENST00000349457.8	TSL:1 MANE Select	c.846C>T	p.Arg282Arg	synonymous	Exon 9 of 12	ENSP00000290823.4
	ADGRG5	ENST00000340339.4	TSL:1	c.846C>T	p.Arg282Arg	synonymous	Exon 9 of 12	ENSP00000342981.4
	ADGRG5	ENST00000394361.8	TSL:2	n.932C>T		non_coding_transcript_exon	Exon 9 of 11

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51844 AN: 151848 Hom.: 9537 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.376 AC: 92964 AN: 247470 AF XY: 0.365

Gnomad AFR exome AF: 0.369

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.705

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.309 AC: 450233 AN: 1458528 Hom.: 76571 Cov.: 36 AF XY: 0.310 AC XY: 225004 AN XY: 725662

African (AFR) AF: 0.375 AC: 12563 AN: 33458

American (AMR) AF: 0.551 AC: 24518 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 8200 AN: 26090

East Asian (EAS) AF: 0.746 AC: 29596 AN: 39652

South Asian (SAS) AF: 0.391 AC: 33652 AN: 86088

European-Finnish (FIN) AF: 0.301 AC: 15492 AN: 51472

Middle Eastern (MID) AF: 0.294 AC: 1693 AN: 5760

European-Non Finnish (NFE) AF: 0.274 AC: 304745 AN: 1111216

Other (OTH) AF: 0.328 AC: 19774 AN: 60326

GnomAD4 genome AF: 0.342 AC: 51908 AN: 151966 Hom.: 9556 Cov.: 32 AF XY: 0.348 AC XY: 25829 AN XY: 74258

African (AFR) AF: 0.370 AC: 15309 AN: 41426

American (AMR) AF: 0.446 AC: 6822 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3635 AN: 5134

South Asian (SAS) AF: 0.407 AC: 1957 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3142 AN: 10584

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18892 AN: 67938

Other (OTH) AF: 0.341 AC: 719 AN: 2110

Alfa AF: 0.307 Hom.: 32481

Bravo AF: 0.355

Asia WGS AF: 0.564 AC: 1962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.6
DANN	Benign	0.57
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9937918; hg19: chr16-57601792; COSMIC: COSV61083434; COSMIC: COSV61083434;