rs182626712

Variant names:

• chr5-90745110-A-C
• rs182626712
• NM_032119.4:c.10614A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-90745110-A-C
• chr5-90745110-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032119.4(ADGRV1):​c.10614A>C​(p.Gln3538His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q3538Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.601
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034571916).

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.10614A>C	p.Gln3538His	missense	Exon 51 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10630A>C		non_coding_transcript_exon	Exon 51 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10614A>C	p.Gln3538His	missense	Exon 51 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.3311A>C		non_coding_transcript_exon	Exon 19 of 26
	ADGRV1	ENST00000640374.1	TSL:5	n.3758A>C		non_coding_transcript_exon	Exon 21 of 27

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0030
DANN	Benign	0.26
DEOGEN2	Benign	0.14	T
Eigen	Benign	-2.9
Eigen_PC	Benign	-3.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.72	T
PhyloP100		-0.60
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.063
Sift	Benign	0.28	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.19
MutPred		0.42		Gain of sheet (P = 0.1208)
MVP		0.085
MPC		0.24
ClinPred		0.11	T
GERP RS		-11
Varity_R		0.071
gMVP		0.62
Mutation Taster		=78/22	polymorphism

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: rs182626712; hg19: chr5-90040927;