NM_201525.4:c.-36+123T>A

Variant names:

• chr16-57628925-T-A
• rs201652072
• NM_201525.4:c.-36+123T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201525.4(ADGRG1):​c.-36+123T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 144,146 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (74 hom., cov: 27)
  • Exomes 𝑓: 0.0025 (122 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.595
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

ENSG00000261633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-57628925-T-A is Benign according to our data. Variant chr16-57628925-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1175599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0996 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.-36+123T>A		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+123T>A		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9044T>A		intron	N/A	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.-36+123T>A		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8789T>A		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+97T>A		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2453 AN: 144036 Hom.: 73 Cov.: 27

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.000444

Gnomad OTH AF: 0.0146

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00255 AC: 1556 AN: 610746 Hom.: 122 Cov.: 7 AF XY: 0.00234 AC XY: 664 AN XY: 284098

African (AFR) AF: 0.0555 AC: 570 AN: 10278

American (AMR) AF: 0.00419 AC: 3 AN: 716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3854

East Asian (EAS) AF: 0.123 AC: 309 AN: 2504

South Asian (SAS) AF: 0.0265 AC: 323 AN: 12202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 214

Middle Eastern (MID) AF: 0.00587 AC: 7 AN: 1192

European-Non Finnish (NFE) AF: 0.000191 AC: 107 AN: 560112

Other (OTH) AF: 0.0120 AC: 237 AN: 19674

GnomAD4 genome AF: 0.0171 AC: 2470 AN: 144146 Hom.: 74 Cov.: 27 AF XY: 0.0180 AC XY: 1263 AN XY: 70320

African (AFR) AF: 0.0435 AC: 1673 AN: 38424

American (AMR) AF: 0.00620 AC: 91 AN: 14670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.107 AC: 513 AN: 4784

South Asian (SAS) AF: 0.0286 AC: 130 AN: 4552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9884

Middle Eastern (MID) AF: 0.0105 AC: 3 AN: 286

European-Non Finnish (NFE) AF: 0.000444 AC: 29 AN: 65286

Other (OTH) AF: 0.0155 AC: 31 AN: 2004

Alfa AF: 0.0125 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.42
PhyloP100		-0.59
PromoterAI		-0.0046	Neutral
Mutation Taster		=100/0	polymorphism

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: rs201652072; hg19: chr16-57662837;