rs6570507

Variant names:

• chr6-142358435-G-A
• rs6570507
• NM_198569.3:c.104-9134G>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.104-9134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,114 control chromosomes in the GnomAD database, including 21,053 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 0.46 (21053 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 79 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.104-9134G>A		intron_variant	Intron 2 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.104-9134G>A		intron_variant	Intron 2 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70186 AN: 151996 Hom.: 20988 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.462 AC: 70319 AN: 152114 Hom.: 21053 Cov.: 32 AF XY: 0.458 AC XY: 34037 AN XY: 74348

African (AFR) AF: 0.860 AC: 35738 AN: 41532

American (AMR) AF: 0.379 AC: 5791 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1025 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2066 AN: 5170

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10570

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19867 AN: 67960

Other (OTH) AF: 0.465 AC: 983 AN: 2116

Alfa AF: 0.346 Hom.: 34579

Bravo AF: 0.485

Asia WGS AF: 0.427 AC: 1482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.20
PhyloP100		-0.22
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: rs6570507; hg19: chr6-142679572;