rs137853918

Variant names:

• chr5-91072567-A-G
• rs137853918
• NM_032119.4:c.18273A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032119.4(ADGRV1):​c.18273A>G​(p.Ala6091Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,613,858 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (31 hom.)
• Consequence: ADGRV1 NM_032119.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:10 O:1
• Conservation: PhyloP100: -0.889
• Publications: 1 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]

LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-91072567-A-G is Benign according to our data. Variant chr5-91072567-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 100602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.889 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0033 (503/152344) while in subpopulation SAS AF = 0.00704 (34/4828). AF 95% confidence interval is 0.00518. There are 0 homozygotes in GnomAd4. There are 283 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR,AD gene

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.18273A>G	p.Ala6091Ala	synonymous	Exon 86 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.18289A>G		non_coding_transcript_exon	Exon 86 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.18273A>G	p.Ala6091Ala	synonymous	Exon 86 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5540A>G		non_coding_transcript_exon	Exon 22 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.7227A>G	p.Ala2409Ala	synonymous	Exon 34 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 504 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00876

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00397

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00407 AC: 1014 AN: 249030 AF XY: 0.00451

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00798

Gnomad NFE exome AF: 0.00384

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00403 AC: 5895 AN: 1461514 Hom.: 31 Cov.: 31 AF XY: 0.00430 AC XY: 3124 AN XY: 727034

African (AFR) AF: 0.000777 AC: 26 AN: 33472

American (AMR) AF: 0.00192 AC: 86 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00906 AC: 781 AN: 86242

European-Finnish (FIN) AF: 0.00691 AC: 369 AN: 53402

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5764

European-Non Finnish (NFE) AF: 0.00395 AC: 4389 AN: 1111728

Other (OTH) AF: 0.00325 AC: 196 AN: 60364

GnomAD4 genome AF: 0.00330 AC: 503 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.00380 AC XY: 283 AN XY: 74484

African (AFR) AF: 0.000745 AC: 31 AN: 41586

American (AMR) AF: 0.00418 AC: 64 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4828

European-Finnish (FIN) AF: 0.00876 AC: 93 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00397 AC: 270 AN: 68026

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00293 Hom.: 1

Bravo AF: 0.00243

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00436

EpiControl AF: 0.00386

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (6)
-	-	4	not specified (4)
-	1	-	Febrile seizures, familial, 4 (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs137853918; hg19: chr5-90368384; COSMIC: COSV67991306;