rs1982395

Variant names:

• chr16-57634844-T-C
• rs1982395
• NM_201525.4:c.-36+6042T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201525.4(ADGRG1):​c.-36+6042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,172 control chromosomes in the GnomAD database, including 28,188 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 0.59 (28188 hom., cov: 33)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+6042T>C		intron_variant	Intron 1 of 13	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+6042T>C		intron_variant	Intron 1 of 13	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89821 AN: 152054 Hom.: 28137 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.591 AC: 89932 AN: 152172 Hom.: 28188 Cov.: 33 AF XY: 0.598 AC XY: 44456 AN XY: 74392

African (AFR) AF: 0.809 AC: 33590 AN: 41540

American (AMR) AF: 0.581 AC: 8883 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1677 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3389 AN: 5178

South Asian (SAS) AF: 0.588 AC: 2839 AN: 4828

European-Finnish (FIN) AF: 0.595 AC: 6299 AN: 10586

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31471 AN: 67976

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

Alfa AF: 0.560 Hom.: 4668

Bravo AF: 0.599

Asia WGS AF: 0.635 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		-0.52
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: rs1982395; hg19: chr16-57668756;