NM_201525.4:c.-36+53A>T

Variant names:

• chr16-57628855-A-T
• rs76652341
• NM_201525.4:c.-36+53A>T

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.-36+53A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 881,016 control chromosomes in the GnomAD database, including 4,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1489 hom., cov: 33)
  • Exomes 𝑓: 0.074 (3274 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.855
• Publications: 2 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

ENSG00000261633 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 16-57628855-A-T is Benign according to our data. Variant chr16-57628855-A-T is described in ClinVar as Benign. ClinVar VariationId is 1227704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 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+53A>T		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+53A>T		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+8974A>T		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+53A>T		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8719A>T		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+27A>T		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20488 AN: 149982 Hom.: 1484 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.0744 AC: 54369 AN: 730918 Hom.: 3274 Cov.: 19 AF XY: 0.0743 AC XY: 25139 AN XY: 338260

African (AFR) AF: 0.107 AC: 1454 AN: 13618

American (AMR) AF: 0.0895 AC: 77 AN: 860

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 405 AN: 4458

East Asian (EAS) AF: 0.117 AC: 347 AN: 2958

South Asian (SAS) AF: 0.0912 AC: 1286 AN: 14100

European-Finnish (FIN) AF: 0.0373 AC: 10 AN: 268

Middle Eastern (MID) AF: 0.101 AC: 135 AN: 1336

European-Non Finnish (NFE) AF: 0.0727 AC: 48695 AN: 669500

Other (OTH) AF: 0.0823 AC: 1960 AN: 23820

GnomAD4 genome AF: 0.137 AC: 20515 AN: 150098 Hom.: 1489 Cov.: 33 AF XY: 0.135 AC XY: 9881 AN XY: 73358

African (AFR) AF: 0.152 AC: 6198 AN: 40764

American (AMR) AF: 0.132 AC: 1993 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 541 AN: 3448

East Asian (EAS) AF: 0.209 AC: 1066 AN: 5094

South Asian (SAS) AF: 0.152 AC: 718 AN: 4710

European-Finnish (FIN) AF: 0.0851 AC: 892 AN: 10476

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8587 AN: 67200

Other (OTH) AF: 0.140 AC: 291 AN: 2078

Alfa AF: 0.128 Hom.: 34

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.85
PromoterAI		0.0082	Neutral
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76652341; hg19: chr16-57662767;