chr6-142309521-A-G

Position:

• chr6-142309521-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_198569.3(ADGRG6):​c.3-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,545,408 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.023 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (124 hom.)
• Consequence: ADGRG6 NM_198569.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.194

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-142309521-A-G is Benign according to our data. Variant chr6-142309521-A-G is described in ClinVar as [Benign]. Clinvar id is 1283634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG6	NM_198569.3	c.3-23A>G		intron_variant		ENST00000367609.8	NP_940971.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG6	ENST00000367609.8	c.3-23A>G		intron_variant		1	NM_198569.3	ENSP00000356581

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3415 AN: 151818 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.0240

GnomAD3 exomes AF: 0.00598 AC: 1331 AN: 222724 Hom.: 30 AF XY: 0.00492 AC XY: 590 AN XY: 119800

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.00458

Gnomad ASJ exome AF: 0.00296

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000548

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00275 AC: 3836 AN: 1393472 Hom.: 124 Cov.: 22 AF XY: 0.00250 AC XY: 1735 AN XY: 694510

Gnomad4 AFR exome AF: 0.0813

Gnomad4 AMR exome AF: 0.00594

Gnomad4 ASJ exome AF: 0.00339

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000397

Gnomad4 OTH exome AF: 0.00717

GnomAD4 genome AF: 0.0225 AC: 3424 AN: 151936 Hom.: 123 Cov.: 32 AF XY: 0.0218 AC XY: 1623 AN XY: 74288

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000590

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0124 Hom.: 10

Bravo AF: 0.0273

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	19
DANN	Benign	0.61
La Branchor		0.86
BranchPoint Hunter		6.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28461686; hg19: chr6-142630658;