rs1329705

Variant names:

• chr6-142432201-G-A
• rs1329705
• NM_198569.3:c.3320-5233G>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.3320-5233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,974 control chromosomes in the GnomAD database, including 2,938 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 0.20 (2938 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.3320-5233G>A		intron_variant	Intron 22 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.3320-5233G>A		intron_variant	Intron 22 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29729 AN: 151856 Hom.: 2936 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.196 AC: 29761 AN: 151974 Hom.: 2938 Cov.: 32 AF XY: 0.196 AC XY: 14546 AN XY: 74248

African (AFR) AF: 0.203 AC: 8427 AN: 41456

American (AMR) AF: 0.200 AC: 3044 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.102 AC: 525 AN: 5158

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4810

European-Finnish (FIN) AF: 0.199 AC: 2093 AN: 10534

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13380 AN: 67982

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.192 Hom.: 4194

Bravo AF: 0.190

Asia WGS AF: 0.202 AC: 701 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		0.011
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: rs1329705; hg19: chr6-142753338;