Genetic Variant ADGRB2:c.4573-13G>A (chr1-31727618-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001364857.2(ADGRB2):c.4573-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,496,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

ADGRB2
NM_001364857.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27

Publications

0 publications found

Variant links:

Genes affected

ADGRB2 (HGNC:944): (adhesion G protein-coupled receptor B2) This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ADGRB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-31727618-C-T is Benign according to our data. Variant chr1-31727618-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1989701.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADGRB2	NM_001364857.2	MANE Select	c.4573-13G>A	intron	N/A	NP_001351786.1	O60241-1
ADGRB2	NM_001294335.2		c.4570-13G>A	intron	N/A	NP_001281264.1	O60241-2
ADGRB2	NM_001294336.2		c.4471-13G>A	intron	N/A	NP_001281265.1	O60241-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADGRB2	ENST00000373658.8	TSL:5 MANE Select	c.4573-13G>A	intron	N/A	ENSP00000362762.3	O60241-1
ADGRB2	ENST00000373655.6	TSL:1	c.4570-13G>A	intron	N/A	ENSP00000362759.2	O60241-2
ADGRB2	ENST00000527361.5	TSL:1	c.4471-13G>A	intron	N/A	ENSP00000435397.1	O60241-4

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000358

AC:

AN:

136688

AF XY:

0.000329

show subpopulations

Gnomad AFR exome

AF:

0.000796

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000242

AC:

325

AN:

1344776

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

140

AN XY:

659520

show subpopulations

African (AFR)

AF:

0.000207

AC:

AN:

29028

American (AMR)

AF:

0.000994

AC:

AN:

24134

Ashkenazi Jewish (ASJ)

AF:

0.0000505

AC:

AN:

19800

East Asian (EAS)

AF:

0.0000550

AC:

AN:

36356

South Asian (SAS)

AF:

0.0000301

AC:

AN:

66474

European-Finnish (FIN)

AF:

0.0000414

AC:

AN:

48290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.000253

AC:

269

AN:

1061418

Other (OTH)

AF:

0.000345

AC:

AN:

55068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000316

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41488

American (AMR)

AF:

0.000720

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

67936

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000536

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.17

(source)

DANN

Benign

0.64

PhyloP100

-1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over