6-142348201-A-G

Variant names:

• chr6-142348201-A-G
• rs9496346
• NM_198569.3:c.104-19368A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198569.3(ADGRG6):​c.104-19368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,884 control chromosomes in the GnomAD database, including 15,185 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 0.41 (15185 hom., cov: 31)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.104-19368A>G		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.104-19368A>G		intron_variant	Intron 2 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62517 AN: 151766 Hom.: 15146 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.412 AC: 62621 AN: 151884 Hom.: 15185 Cov.: 31 AF XY: 0.410 AC XY: 30442 AN XY: 74254

African (AFR) AF: 0.683 AC: 28273 AN: 41396

American (AMR) AF: 0.361 AC: 5507 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3462

East Asian (EAS) AF: 0.409 AC: 2112 AN: 5164

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4814

European-Finnish (FIN) AF: 0.269 AC: 2840 AN: 10554

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19958 AN: 67914

Other (OTH) AF: 0.425 AC: 894 AN: 2104

Alfa AF: 0.337 Hom.: 5093

Bravo AF: 0.429

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		0.62
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: rs9496346; hg19: chr6-142669338;