Genetic Variant NM_001083909.3:c.255+47G>A (chr10-133098810-G-A) – 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.255+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,576,698 control chromosomes in the GnomAD database, including 22,799 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 0.14 ( 1697 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21102 hom. )

Consequence

ADGRA1
NM_001083909.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.427

Publications

9 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3 link	c.255+47G>A	intron_variant	Intron 4 of 6	ENST00000392607.8	NP_001077378.1	Q86SQ6-3
ADGRA1	XM_011540273.1 link	c.-107+47G>A	intron_variant	Intron 1 of 2		XP_011538575.1
ADGRA1	XM_017016779.2 link	c.255+47G>A	intron_variant	Intron 3 of 4		XP_016872268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8 link	c.255+47G>A		intron_variant	Intron 4 of 6	5	NM_001083909.3	ENSP00000376384.3		Q86SQ6-3

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21735

AN:

152174

Hom.:

1696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.151

AC:

34055

AN:

225294

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.0985

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.169

AC:

240073

AN:

1424406

Hom.:

21102

Cov.:

AF XY:

0.168

AC XY:

118772

AN XY:

706348

show subpopulations

African (AFR)

AF:

0.0842

AC:

2706

AN:

32134

American (AMR)

AF:

0.102

AC:

4005

AN:

39404

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5161

AN:

24922

East Asian (EAS)

AF:

0.0882

AC:

3451

AN:

39110

South Asian (SAS)

AF:

0.124

AC:

10323

AN:

82990

European-Finnish (FIN)

AF:

0.167

AC:

7450

AN:

44652

Middle Eastern (MID)

AF:

0.161

AC:

905

AN:

5616

European-Non Finnish (NFE)

AF:

0.179

AC:

196247

AN:

1096544

Other (OTH)

AF:

0.166

AC:

9825

AN:

59034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9381

18762

28143

37524

46905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21743

AN:

152292

Hom.:

1697

Cov.:

AF XY:

0.141

AC XY:

10536

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0810

AC:

3366

AN:

41572

American (AMR)

AF:

0.141

AC:

2153

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

751

AN:

3470

East Asian (EAS)

AF:

0.106

AC:

550

AN:

5188

South Asian (SAS)

AF:

0.121

AC:

585

AN:

4826

European-Finnish (FIN)

AF:

0.160

AC:

1693

AN:

10602

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.178

AC:

12136

AN:

68014

Other (OTH)

AF:

0.167

AC:

353

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

996

1992

2989

3985

4981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.154

Hom.:

1188

Bravo

AF:

0.141

Asia WGS

AF:

0.103

AC:

362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.9

(source)

DANN

Benign

0.77

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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NM_001083909.3:c.255+47G>A

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