NM_032119.4:c.327C>T

Variant names:

• chr5-90617923-C-T
• rs61753944
• NM_032119.4:c.327C>T

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.327C>T​(p.Asp109Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,584,912 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (108 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (98 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.07
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 5-90617923-C-T is Benign according to our data. Variant chr5-90617923-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 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.327C>T	p.Asp109Asp	synonymous	Exon 3 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.426C>T		non_coding_transcript_exon	Exon 3 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.327C>T	p.Asp109Asp	synonymous	Exon 3 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000640281.1	TSL:1	n.386C>T		non_coding_transcript_exon	Exon 3 of 7
	ADGRV1	ENST00000508842.5	TSL:3	c.339C>T	p.Asp113Asp	synonymous	Exon 3 of 4	ENSP00000425936.1	D6RIF0

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3367 AN: 152048 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.00865

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00537 AC: 1097 AN: 204438 AF XY: 0.00427

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.000545

Gnomad EAS exome AF: 0.00149

Gnomad FIN exome AF: 0.000103

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00264 AC: 3787 AN: 1432746 Hom.: 98 Cov.: 30 AF XY: 0.00237 AC XY: 1683 AN XY: 709656

African (AFR) AF: 0.0729 AC: 2404 AN: 32972

American (AMR) AF: 0.00382 AC: 155 AN: 40620

Ashkenazi Jewish (ASJ) AF: 0.000548 AC: 14 AN: 25526

East Asian (EAS) AF: 0.000410 AC: 16 AN: 39000

South Asian (SAS) AF: 0.000392 AC: 32 AN: 81530

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51888

Middle Eastern (MID) AF: 0.00576 AC: 33 AN: 5730

European-Non Finnish (NFE) AF: 0.000701 AC: 768 AN: 1096096

Other (OTH) AF: 0.00613 AC: 364 AN: 59384

GnomAD4 genome AF: 0.0222 AC: 3373 AN: 152166 Hom.: 108 Cov.: 32 AF XY: 0.0219 AC XY: 1632 AN XY: 74416

African (AFR) AF: 0.0750 AC: 3112 AN: 41498

American (AMR) AF: 0.00864 AC: 132 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 67998

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00967 Hom.: 36

Bravo AF: 0.0254

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (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	-0.33
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		1.1
Mutation Taster		=96/4	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: rs61753944; hg19: chr5-89913740; COSMIC: COSV67980701;