rs77469944

Variant names:

• chr5-91150072-A-G
• rs77469944
• NM_032119.4:c.18475A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.18475A>G​(p.Met6159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,552,142 control chromosomes in the GnomAD database, including 1,108 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M6159I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.042 (366 hom., cov: 30)
  • Exomes 𝑓: 0.012 (742 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 3.41
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017308891).
• BP6: Variant 5-91150072-A-G is Benign according to our data. Variant chr5-91150072-A-G is described in ClinVar as Benign. ClinVar VariationId is 46298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

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.18475A>G	p.Met6159Val	missense	Exon 88 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.18491A>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.18475A>G	p.Met6159Val	missense	Exon 88 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5742A>G		non_coding_transcript_exon	Exon 24 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.7429A>G	p.Met2477Val	missense	Exon 36 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6329 AN: 150442 Hom.: 364 Cov.: 30

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00578

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.0309

GnomAD2 exomes AF: 0.0265 AC: 4328 AN: 163388 AF XY: 0.0288

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00840

Gnomad ASJ exome AF: 0.00511

Gnomad EAS exome AF: 0.0447

Gnomad FIN exome AF: 0.00140

Gnomad NFE exome AF: 0.00277

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0119 AC: 16652 AN: 1401586 Hom.: 742 Cov.: 34 AF XY: 0.0138 AC XY: 9526 AN XY: 691652

African (AFR) AF: 0.131 AC: 4151 AN: 31630

American (AMR) AF: 0.0110 AC: 393 AN: 35878

Ashkenazi Jewish (ASJ) AF: 0.00529 AC: 133 AN: 25130

East Asian (EAS) AF: 0.0275 AC: 992 AN: 36052

South Asian (SAS) AF: 0.0862 AC: 6812 AN: 79058

European-Finnish (FIN) AF: 0.00137 AC: 68 AN: 49636

Middle Eastern (MID) AF: 0.0153 AC: 87 AN: 5688

European-Non Finnish (NFE) AF: 0.00256 AC: 2766 AN: 1080360

Other (OTH) AF: 0.0215 AC: 1250 AN: 58154

GnomAD4 genome AF: 0.0422 AC: 6354 AN: 150556 Hom.: 366 Cov.: 30 AF XY: 0.0418 AC XY: 3069 AN XY: 73378

African (AFR) AF: 0.127 AC: 5176 AN: 40862

American (AMR) AF: 0.0168 AC: 254 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 20 AN: 3462

East Asian (EAS) AF: 0.0443 AC: 227 AN: 5120

South Asian (SAS) AF: 0.0807 AC: 385 AN: 4768

European-Finnish (FIN) AF: 0.00158 AC: 16 AN: 10136

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00251 AC: 170 AN: 67798

Other (OTH) AF: 0.0306 AC: 63 AN: 2062

Alfa AF: 0.0188 Hom.: 332

Bravo AF: 0.0469

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.119 AC: 445

ESP6500EA AF: 0.00208 AC: 17

ExAC AF: 0.0213 AC: 2440

Asia WGS AF: 0.0620 AC: 214 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.98	T
PhyloP100		3.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.099
Sift	Benign	0.057	T
Sift4G	Uncertain	0.030	D
Polyphen		0.0	B
Vest4		0.21
MPC		0.048
ClinPred		0.014	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs77469944; hg19: chr5-90445889;