Genetic Variant ADGRA1:c.-100A>G (chr10-133088810-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001083909.3(ADGRA1):c.-100A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,233,776 control chromosomes in the GnomAD database, including 188,776 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 0.64 ( 32756 hom., cov: 36)

Exomes 𝑓: 0.53 ( 156020 hom. )

Consequence

ADGRA1
NM_001083909.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.124

Publications

7 publications found

Variant links:

Genes affected

ADGRA1 (HGNC:13838): (adhesion G protein-coupled receptor A1) This gene encodes a protein that belongs to the adhesion family of G-protein-coupled receptors. Members of this family function in several sensory systems and regulate blood pressure, immune responses, food intake and development. A similar protein in rodents is thought to play a role in in the regulation of neuronal signaling pathways. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Mar 2014]

ADGRA1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3 link	c.-100A>G		5_prime_UTR_variant	Exon 2 of 7	ENST00000392607.8	NP_001077378.1	Q86SQ6-3
ADGRA1	XM_017016779.2 link	c.-100A>G		5_prime_UTR_variant	Exon 1 of 5		XP_016872268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8 link	c.-100A>G		5_prime_UTR_variant	Exon 2 of 7	5	NM_001083909.3	ENSP00000376384.3		Q86SQ6-3

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96802

AN:

152102

Hom.:

32694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.872

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.532

AC:

575733

AN:

1081564

Hom.:

156020

Cov.:

AF XY:

0.533

AC XY:

272047

AN XY:

510740

show subpopulations

African (AFR)

AF:

0.895

AC:

20576

AN:

22990

American (AMR)

AF:

0.599

AC:

5040

AN:

8414

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

7503

AN:

14376

East Asian (EAS)

AF:

0.765

AC:

20294

AN:

26512

South Asian (SAS)

AF:

0.635

AC:

12386

AN:

19496

European-Finnish (FIN)

AF:

0.520

AC:

11685

AN:

22490

Middle Eastern (MID)

AF:

0.567

AC:

2090

AN:

3686

European-Non Finnish (NFE)

AF:

0.512

AC:

471324

AN:

919856

Other (OTH)

AF:

0.568

AC:

24835

AN:

43744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14332

28664

42996

57328

71660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.637

AC:

96921

AN:

152212

Hom.:

32756

Cov.:

AF XY:

0.637

AC XY:

47393

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.872

AC:

36264

AN:

41574

American (AMR)

AF:

0.617

AC:

9444

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1824

AN:

3472

East Asian (EAS)

AF:

0.731

AC:

3763

AN:

5146

South Asian (SAS)

AF:

0.640

AC:

3089

AN:

4828

European-Finnish (FIN)

AF:

0.523

AC:

5540

AN:

10602

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35053

AN:

67976

Other (OTH)

AF:

0.640

AC:

1351

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.578

Hom.:

3316

Bravo

AF:

0.656

Asia WGS

AF:

0.681

AC:

2363

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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10-133088810-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over