chr5-90784003-A-G

Variant names:

• chr5-90784003-A-G
• rs17554631
• NM_032119.4:c.13599A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.13599A>G​(p.Thr4533Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,610,940 control chromosomes in the GnomAD database, including 34,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2448 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32520 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.430
• 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]

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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-90784003-A-G is Benign according to our data. Variant chr5-90784003-A-G is described in ClinVar as Benign. ClinVar VariationId is 46268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 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.13599A>G	p.Thr4533Thr	synonymous	Exon 67 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.13615A>G		non_coding_transcript_exon	Exon 67 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.13599A>G	p.Thr4533Thr	synonymous	Exon 67 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.866A>G		non_coding_transcript_exon	Exon 3 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.2553A>G	p.Thr851Thr	synonymous	Exon 15 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23447 AN: 152000 Hom.: 2447 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.162 AC: 40096 AN: 246750 AF XY: 0.165

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.0963

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.00291

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.201 AC: 293874 AN: 1458822 Hom.: 32520 Cov.: 32 AF XY: 0.199 AC XY: 144460 AN XY: 725636

African (AFR) AF: 0.0342 AC: 1144 AN: 33460

American (AMR) AF: 0.102 AC: 4554 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3725 AN: 26102

East Asian (EAS) AF: 0.00184 AC: 73 AN: 39662

South Asian (SAS) AF: 0.103 AC: 8870 AN: 85986

European-Finnish (FIN) AF: 0.270 AC: 14396 AN: 53312

Middle Eastern (MID) AF: 0.140 AC: 805 AN: 5740

European-Non Finnish (NFE) AF: 0.225 AC: 249450 AN: 1109728

Other (OTH) AF: 0.180 AC: 10857 AN: 60274

GnomAD4 genome AF: 0.154 AC: 23449 AN: 152118 Hom.: 2448 Cov.: 32 AF XY: 0.154 AC XY: 11444 AN XY: 74356

African (AFR) AF: 0.0403 AC: 1672 AN: 41520

American (AMR) AF: 0.139 AC: 2130 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3466

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5190

South Asian (SAS) AF: 0.102 AC: 494 AN: 4826

European-Finnish (FIN) AF: 0.279 AC: 2950 AN: 10574

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15183 AN: 67956

Other (OTH) AF: 0.169 AC: 355 AN: 2106

Alfa AF: 0.183 Hom.: 5334

Bravo AF: 0.138

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Usher syndrome type 2C (2)
-	-	1	Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.72
PhyloP100		-0.43
Mutation Taster		=93/7	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: rs17554631; hg19: chr5-90079820;