rs10852554

Variant names:

• chr16-57663620-T-G
• rs10852554
• NM_201525.4:c.*38T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201525.4(ADGRG1):​c.*38T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,604,006 control chromosomes in the GnomAD database, including 442,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46083 hom., cov: 35)
  • Exomes 𝑓: 0.74 (395934 hom.)
• Consequence: ADGRG1 NM_201525.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.550
• Publications: 14 publications found

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000306939 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-57663620-T-G is Benign according to our data. Variant chr16-57663620-T-G is described in ClinVar as Benign. ClinVar VariationId is 259865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	NM_201525.4	MANE Select	c.*38T>G		3_prime_UTR	Exon 14 of 14	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.*38T>G		3_prime_UTR	Exon 15 of 15	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.*38T>G		3_prime_UTR	Exon 15 of 15	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.*38T>G		3_prime_UTR	Exon 14 of 14	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.*38T>G		3_prime_UTR	Exon 15 of 15	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.*38T>G		3_prime_UTR	Exon 15 of 15	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117310 AN: 152120 Hom.: 46031 Cov.: 35

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.760 AC: 186247 AN: 245194 AF XY: 0.755

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.943

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.733

GnomAD4 exome AF: 0.736 AC: 1067830 AN: 1451768 Hom.: 395934 Cov.: 37 AF XY: 0.736 AC XY: 532383 AN XY: 722884

African (AFR) AF: 0.888 AC: 29669 AN: 33422

American (AMR) AF: 0.840 AC: 37532 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17363 AN: 26098

East Asian (EAS) AF: 0.948 AC: 37603 AN: 39680

South Asian (SAS) AF: 0.811 AC: 69907 AN: 86160

European-Finnish (FIN) AF: 0.596 AC: 28011 AN: 46962

Middle Eastern (MID) AF: 0.740 AC: 4254 AN: 5750

European-Non Finnish (NFE) AF: 0.720 AC: 798295 AN: 1108792

Other (OTH) AF: 0.751 AC: 45196 AN: 60200

GnomAD4 genome AF: 0.771 AC: 117420 AN: 152238 Hom.: 46083 Cov.: 35 AF XY: 0.767 AC XY: 57079 AN XY: 74422

African (AFR) AF: 0.886 AC: 36836 AN: 41566

American (AMR) AF: 0.808 AC: 12363 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2300 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4877 AN: 5172

South Asian (SAS) AF: 0.820 AC: 3960 AN: 4828

European-Finnish (FIN) AF: 0.575 AC: 6086 AN: 10586

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48603 AN: 67990

Other (OTH) AF: 0.764 AC: 1616 AN: 2116

Alfa AF: 0.734 Hom.: 11619

Bravo AF: 0.795

Asia WGS AF: 0.861 AC: 2994 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Bilateral frontoparietal polymicrogyria (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-0.55
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: rs10852554; hg19: chr16-57697532; COSMIC: COSV59650806; COSMIC: COSV59650806;