6-142385996-T-G

Variant names:

• chr6-142385996-T-G
• rs6937121
• NM_198569.3:c.1222+2153T>G

Variant summary

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

The NM_198569.3(ADGRG6):​c.1222+2153T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,008 control chromosomes in the GnomAD database, including 20,538 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 (20538 hom., cov: 32)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 15 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 = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.1222+2153T>G		intron_variant	Intron 6 of 24	ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.1222+2153T>G		intron_variant	Intron 6 of 24	1	NM_198569.3	ENSP00000356581.3
ADGRG6	ENST00000367608.6	c.1138+3977T>G		intron_variant	Intron 5 of 23	1		ENSP00000356580.2
ADGRG6	ENST00000230173.10	c.1222+2153T>G		intron_variant	Intron 6 of 25	1		ENSP00000230173.6
ADGRG6	ENST00000296932.13	c.1138+3977T>G		intron_variant	Intron 5 of 24	1		ENSP00000296932.8

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69745 AN: 151890 Hom.: 20475 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.460 AC: 69876 AN: 152008 Hom.: 20538 Cov.: 32 AF XY: 0.455 AC XY: 33821 AN XY: 74304

African (AFR) AF: 0.844 AC: 35030 AN: 41494

American (AMR) AF: 0.382 AC: 5826 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2127 AN: 5178

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2850 AN: 10572

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

European-Non Finnish (NFE) AF: 0.294 AC: 19976 AN: 67918

Other (OTH) AF: 0.468 AC: 986 AN: 2106

Alfa AF: 0.374 Hom.: 18469

Bravo AF: 0.484

Asia WGS AF: 0.446 AC: 1544 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.39
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: rs6937121; hg19: chr6-142707133;