rs200111522

Variant names:

• chr5-91150067-A-G
• rs200111522
• NM_032119.4:c.18470A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_032119.4(ADGRV1):​c.18470A>G​(p.Asn6157Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,548,810 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (5 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 8.72
• Publications: 2 publications found

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]

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

ACMG classification

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

• BP6: Variant 5-91150067-A-G is Benign according to our data. Variant chr5-91150067-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.18470A>G	p.Asn6157Ser	missense	Exon 88 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.18486A>G		non_coding_transcript_exon	Exon 88 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.18470A>G	p.Asn6157Ser	missense	Exon 88 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5737A>G		non_coding_transcript_exon	Exon 24 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.7424A>G	p.Asn2475Ser	missense	Exon 36 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 108 AN: 149276 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0000495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.000495

GnomAD2 exomes AF: 0.00164 AC: 264 AN: 160834 AF XY: 0.00157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.0250

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00290

GnomAD4 exome AF: 0.000660 AC: 924 AN: 1399534 Hom.: 5 Cov.: 34 AF XY: 0.000646 AC XY: 446 AN XY: 690552

African (AFR) AF: 0.00 AC: 0 AN: 31582

American (AMR) AF: 0.000531 AC: 19 AN: 35774

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 586 AN: 25074

East Asian (EAS) AF: 0.00 AC: 0 AN: 35892

South Asian (SAS) AF: 0.0000633 AC: 5 AN: 79006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49416

Middle Eastern (MID) AF: 0.00282 AC: 16 AN: 5682

European-Non Finnish (NFE) AF: 0.000164 AC: 177 AN: 1079068

Other (OTH) AF: 0.00208 AC: 121 AN: 58040

GnomAD4 genome AF: 0.000723 AC: 108 AN: 149276 Hom.: 2 Cov.: 31 AF XY: 0.000662 AC XY: 48 AN XY: 72540

African (AFR) AF: 0.0000495 AC: 2 AN: 40380

American (AMR) AF: 0.0000669 AC: 1 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67652

Other (OTH) AF: 0.000495 AC: 1 AN: 2020

Alfa AF: 0.00144 Hom.: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00123 AC: 10

ExAC AF: 0.000792 AC: 89

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	ADGRV1-related disorder (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-0.82	T
PhyloP100		8.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.73
MPC		0.17
ClinPred		0.040	T
GERP RS		5.9
Varity_R		0.34
gMVP		0.32
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200111522; hg19: chr5-90445884;