rs16869042

Variant names:

• chr5-90725106-T-G
• rs16869042
• NM_032119.4:c.9927T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-90725106-T-G
• chr5-90725106-T-A
• chr5-90725106-T-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032119.4(ADGRV1):​c.9927T>G​(p.Pro3309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,533,190 control chromosomes in the GnomAD database, including 90,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8211 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82065 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.0120
• Publications: 20 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.017).
• BP6: Variant 5-90725106-T-G is Benign according to our data. Variant chr5-90725106-T-G is described in ClinVar as Benign. ClinVar VariationId is 46409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.012 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 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.9927T>G	p.Pro3309Pro	synonymous	Exon 47 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.9943T>G		non_coding_transcript_exon	Exon 47 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.9927T>G	p.Pro3309Pro	synonymous	Exon 47 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000509621.1	TSL:1	n.2624T>G		non_coding_transcript_exon	Exon 15 of 26
	ADGRV1	ENST00000640374.1	TSL:5	n.3071T>G		non_coding_transcript_exon	Exon 17 of 27

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48357 AN: 151878 Hom.: 8197 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.346 AC: 73643 AN: 212900 AF XY: 0.342

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.340 AC: 469218 AN: 1381196 Hom.: 82065 Cov.: 27 AF XY: 0.338 AC XY: 233051 AN XY: 689078

African (AFR) AF: 0.206 AC: 6250 AN: 30274

American (AMR) AF: 0.551 AC: 17125 AN: 31094

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 6815 AN: 24390

East Asian (EAS) AF: 0.436 AC: 16955 AN: 38888

South Asian (SAS) AF: 0.320 AC: 24707 AN: 77174

European-Finnish (FIN) AF: 0.339 AC: 17983 AN: 52970

Middle Eastern (MID) AF: 0.278 AC: 1537 AN: 5526

European-Non Finnish (NFE) AF: 0.337 AC: 358532 AN: 1063362

Other (OTH) AF: 0.336 AC: 19314 AN: 57518

GnomAD4 genome AF: 0.318 AC: 48376 AN: 151994 Hom.: 8211 Cov.: 32 AF XY: 0.321 AC XY: 23862 AN XY: 74286

African (AFR) AF: 0.219 AC: 9102 AN: 41500

American (AMR) AF: 0.482 AC: 7366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1993 AN: 5160

South Asian (SAS) AF: 0.316 AC: 1525 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3516 AN: 10550

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22741 AN: 67918

Other (OTH) AF: 0.351 AC: 740 AN: 2106

Alfa AF: 0.293 Hom.: 2974

Bravo AF: 0.333

Asia WGS AF: 0.339 AC: 1174 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		-0.012
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: rs16869042; hg19: chr5-90020923; COSMIC: COSV67980903;