rs4896582

chr6-142382740-G-A

Variant summary

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

The NM_198569.3(ADGRG6):c.1138+721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,934 control chromosomes in the GnomAD database, including 23,315 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 0.50 (23315 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG6	NM_198569.3	c.1138+721G>A		intron_variant		ENST00000367609.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG6	ENST00000367609.8	c.1138+721G>A		intron_variant		1	NM_198569.3
ADGRG6	ENST00000230173.10	c.1138+721G>A		intron_variant		1
ADGRG6	ENST00000296932.13	c.1138+721G>A		intron_variant		1
ADGRG6	ENST00000367608.6	c.1138+721G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75135 AN: 151816 Hom.: 23254 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.495 AC: 75265 AN: 151934 Hom.: 23315 Cov.: 32 AF XY: 0.494 AC XY: 36661 AN XY: 74224

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.505

Alfa AF: 0.353 Hom.: 17735

Bravo AF: 0.527

Asia WGS AF: 0.576 AC: 1998 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.069
Dann	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs4896582; hg19: chr6-142703877;