rs6570508

Variant names:

• chr6-142392705-G-A
• rs6570508
• NM_198569.3:c.1309-243G>A

Variant summary

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

The NM_198569.3(ADGRG6):​c.1309-243G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,710 control chromosomes in the GnomAD database, including 23,282 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 (23282 hom., cov: 31)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 12 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=-0.93).
• 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 rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.1309-243G>A		intron_variant	Intron 7 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.1309-243G>A		intron_variant	Intron 7 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75045 AN: 151592 Hom.: 23218 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.287

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: 0.496 AC: 75178 AN: 151710 Hom.: 23282 Cov.: 31 AF XY: 0.494 AC XY: 36620 AN XY: 74138

African (AFR) AF: 0.867 AC: 35901 AN: 41430

American (AMR) AF: 0.458 AC: 6975 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1167 AN: 3462

East Asian (EAS) AF: 0.756 AC: 3905 AN: 5164

South Asian (SAS) AF: 0.361 AC: 1735 AN: 4812

European-Finnish (FIN) AF: 0.287 AC: 3022 AN: 10542

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20965 AN: 67776

Other (OTH) AF: 0.506 AC: 1066 AN: 2106

Alfa AF: 0.379 Hom.: 21590

Bravo AF: 0.528

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.15
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6570508; hg19: chr6-142713842;