Genetic Variant ADGRV1:p.Gly6173Gly (chr5-91150116-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_032119.4(ADGRV1):c.18519G>T(p.Gly6173Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,582,630 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G6173G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.135

Publications

0 publications found

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 links:

LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)

LUCAT1 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=-0.58).

BP6

Variant 5-91150116-G-T is Benign according to our data. Variant chr5-91150116-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 505692.

BP7

Synonymous conserved (PhyloP=0.135 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.18519G>T	p.Gly6173Gly	synonymous	Exon 88 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.18535G>T		non_coding_transcript_exon	Exon 88 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.18519G>T	p.Gly6173Gly	synonymous	Exon 88 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000638510.1	TSL:1	n.5786G>T		non_coding_transcript_exon	Exon 24 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.7473G>T	p.Gly2491Gly	synonymous	Exon 36 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

204924

AF XY:

0.0000183

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000334

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1430994

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

708902

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32746

American (AMR)

AF:

0.0000250

AC:

AN:

40076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25444

East Asian (EAS)

AF:

0.00

AC:

AN:

38326

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0000246

AC:

AN:

1096314

Other (OTH)

AF:

0.0000169

AC:

AN:

59278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151636

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

73984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41264

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67940

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000282

Hom.:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.0

(source)

DANN

Benign

0.62

PhyloP100

0.14

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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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