rs3748069

Variant names:

• chr6-142446496-A-G
• rs3748069
• NM_198569.3:c.*2981A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-142446496-A-G
• chr6-142446496-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198569.3(ADGRG6):​c.*2981A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,036 control chromosomes in the GnomAD database, including 13,122 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 0.39 (13122 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817
• Publications: 42 publications found

Genes affected

ADGRG6 (HGNC:13841): (adhesion G protein-coupled receptor G6) This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person's stature. Multiple transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Mar 2009]

ADGRG6 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.*2981A>G		downstream_gene_variant		ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.*2981A>G		downstream_gene_variant		1	NM_198569.3	ENSP00000356581.3
ADGRG6	ENST00000367608.6	c.*2981A>G		downstream_gene_variant		1		ENSP00000356580.2
ADGRG6	ENST00000230173.10	c.*3114A>G		downstream_gene_variant		1		ENSP00000230173.6
ADGRG6	ENST00000296932.13	c.*3114A>G		downstream_gene_variant		1		ENSP00000296932.8

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59401 AN: 151918 Hom.: 13092 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.391 AC: 59488 AN: 152036 Hom.: 13122 Cov.: 32 AF XY: 0.389 AC XY: 28873 AN XY: 74298

African (AFR) AF: 0.605 AC: 25091 AN: 41452

American (AMR) AF: 0.358 AC: 5468 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2044 AN: 5160

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4818

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10586

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20064 AN: 67958

Other (OTH) AF: 0.419 AC: 884 AN: 2112

Alfa AF: 0.329 Hom.: 41742

Bravo AF: 0.405

Asia WGS AF: 0.430 AC: 1492 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3748069; hg19: chr6-142767633;