NM_198569.3:c.104-17844C>A

Variant names:

• chr6-142349725-C-A
• rs7774095
• NM_198569.3:c.104-17844C>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.104-17844C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,648 control chromosomes in the GnomAD database, including 11,098 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 0.37 (11098 hom., cov: 31)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.104-17844C>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.104-17844C>A		intron_variant	Intron 2 of 24	1	NM_198569.3	ENSP00000356581.3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55531 AN: 151534 Hom.: 11068 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.367 AC: 55616 AN: 151648 Hom.: 11098 Cov.: 31 AF XY: 0.366 AC XY: 27129 AN XY: 74062

African (AFR) AF: 0.537 AC: 22185 AN: 41316

American (AMR) AF: 0.339 AC: 5170 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1969 AN: 5126

South Asian (SAS) AF: 0.317 AC: 1524 AN: 4812

European-Finnish (FIN) AF: 0.269 AC: 2819 AN: 10486

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19736 AN: 67892

Other (OTH) AF: 0.377 AC: 790 AN: 2098

Alfa AF: 0.364 Hom.: 2594

Bravo AF: 0.377

Asia WGS AF: 0.393 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.22
PhyloP100		0.16
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: rs7774095; hg19: chr6-142670862;