Variant 10-133098722-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083909.3(ADGRA1):c.214G>A(p.Gly72Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,611,812 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 98 hom. )

Consequence

ADGRA1
NM_001083909.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077542365).

BP6

Variant 10-133098722-G-A is Benign according to our data. Variant chr10-133098722-G-A is described in ClinVar as [Benign]. Clinvar id is 778418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA1	NM_001083909.3 linkuse as main transcript	c.214G>A	p.Gly72Ser	missense_variant	4/7	ENST00000392607.8
ADGRA1	XM_017016779.2 linkuse as main transcript	c.214G>A	p.Gly72Ser	missense_variant	3/5
ADGRA1	XM_011540273.1 linkuse as main transcript	c.-148G>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8 linkuse as main transcript	c.214G>A	p.Gly72Ser	missense_variant	4/7	5	NM_001083909.3	P1	Q86SQ6-3

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3066

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00909

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00556

AC:

1387

AN:

249588

Hom.:

AF XY:

0.00405

AC XY:

547

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.0723

Gnomad AMR exome

AF:

0.00406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00242

AC:

3535

AN:

1459454

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

1525

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.0768

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.0201

AC:

3068

AN:

152358

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1421

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0689

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.0238

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0706

AC:

311

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00663

AC:

805

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.9

.;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;B

Vest4

0.63

MVP

0.61

MPC

0.48

ClinPred

0.13

GERP RS

4.3

Varity_R

0.80

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over