rs2366928

Variant names:

• chr5-90728918-G-A
• rs2366928
• NM_032119.4:c.10411G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-90728918-G-A
• chr5-90728918-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.10411G>A​(p.Glu3471Lys) variant causes a missense change. The variant allele was found at a frequency of 0.711 in 1,605,000 control chromosomes in the GnomAD database, including 409,901 homozygotes. In-silico tool predicts 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. E3471R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.77 (45573 hom., cov: 32)
  • Exomes 𝑓: 0.71 (364328 hom.)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 4.39
• Publications: 40 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]

ADGRV1 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 2C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• febrile seizures, familial, 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

LOC105379077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 5-90728918-G-A is Benign according to our data. Variant chr5-90728918-G-A is described in ClinVar as Benign. ClinVar VariationId is 46248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 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.10411G>A	p.Glu3471Lys	missense	Exon 49 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10427G>A		non_coding_transcript_exon	Exon 49 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10411G>A	p.Glu3471Lys	missense	Exon 49 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.3108G>A		non_coding_transcript_exon	Exon 17 of 26
	ADGRV1	ENST00000640374.1	TSL:5	n.3555G>A		non_coding_transcript_exon	Exon 19 of 27

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116702 AN: 152048 Hom.: 45497 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.763

GnomAD2 exomes AF: 0.750 AC: 185376 AN: 247166 AF XY: 0.745

Gnomad AFR exome AF: 0.909

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.720

Gnomad EAS exome AF: 0.785

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.728

GnomAD4 exome AF: 0.705 AC: 1024823 AN: 1452834 Hom.: 364328 Cov.: 32 AF XY: 0.707 AC XY: 511177 AN XY: 722816

African (AFR) AF: 0.908 AC: 30176 AN: 33228

American (AMR) AF: 0.846 AC: 37634 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 18808 AN: 26042

East Asian (EAS) AF: 0.804 AC: 31845 AN: 39620

South Asian (SAS) AF: 0.814 AC: 69872 AN: 85794

European-Finnish (FIN) AF: 0.727 AC: 38796 AN: 53342

Middle Eastern (MID) AF: 0.728 AC: 3418 AN: 4694

European-Non Finnish (NFE) AF: 0.679 AC: 750592 AN: 1105636

Other (OTH) AF: 0.728 AC: 43682 AN: 59972

GnomAD4 genome AF: 0.768 AC: 116841 AN: 152166 Hom.: 45573 Cov.: 32 AF XY: 0.774 AC XY: 57609 AN XY: 74398

African (AFR) AF: 0.903 AC: 37491 AN: 41534

American (AMR) AF: 0.805 AC: 12294 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2523 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4152 AN: 5180

South Asian (SAS) AF: 0.815 AC: 3933 AN: 4824

European-Finnish (FIN) AF: 0.733 AC: 7754 AN: 10584

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46260 AN: 67978

Other (OTH) AF: 0.766 AC: 1618 AN: 2112

Alfa AF: 0.717 Hom.: 127588

Bravo AF: 0.779

TwinsUK AF: 0.676 AC: 2508

ALSPAC AF: 0.693 AC: 2669

ESP6500AA AF: 0.904 AC: 3307

ESP6500EA AF: 0.686 AC: 5602

ExAC AF: 0.748 AC: 90266

Asia WGS AF: 0.847 AC: 2943 AN: 3478

EpiCase AF: 0.694

EpiControl AF: 0.691

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	2	Usher syndrome type 2C (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.31
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	6.6e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		4.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.084
MPC		0.052
ClinPred		0.0083	T
GERP RS		5.6
Varity_R		0.055
gMVP		0.34
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.30		Position offset: 15

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

Other links and lift over

dbSNP: rs2366928; hg19: chr5-90024735; COSMIC: COSV67996986; COSMIC: COSV67996986;