5-91153214-T-C

Variant names:

• chr5-91153214-T-C
• rs7726023
• NM_032119.4:c.18625-7T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032119.4(ADGRV1):​c.18625-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,597,782 control chromosomes in the GnomAD database, including 695,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63388 hom., cov: 30)
  • Exomes 𝑓: 0.93 (631747 hom.)
• Consequence: ADGRV1 NM_032119.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002895
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.172
• 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]

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

LOC107986432 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-91153214-T-C is Benign according to our data. Variant chr5-91153214-T-C is described in ClinVar as Benign. ClinVar VariationId is 46299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 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.18625-7T>C		splice_region intron	N/A	NP_115495.3
	ADGRV1	NR_003149.2		n.18641-7T>C		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.18625-7T>C		splice_region intron	N/A	ENSP00000384582.2
	ADGRV1	ENST00000638510.1	TSL:1	n.5892-7T>C		splice_region intron	N/A
	ADGRV1	ENST00000425867.3	TSL:5	c.7579-7T>C		splice_region intron	N/A	ENSP00000392618.3

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138624 AN: 151996 Hom.: 63341 Cov.: 30

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.919

GnomAD2 exomes AF: 0.925 AC: 208936 AN: 225886 AF XY: 0.926

Gnomad AFR exome AF: 0.859

Gnomad AMR exome AF: 0.921

Gnomad ASJ exome AF: 0.935

Gnomad EAS exome AF: 0.895

Gnomad FIN exome AF: 0.927

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.926

GnomAD4 exome AF: 0.935 AC: 1351154 AN: 1445668 Hom.: 631747 Cov.: 37 AF XY: 0.935 AC XY: 670723 AN XY: 717512

African (AFR) AF: 0.863 AC: 28474 AN: 33000

American (AMR) AF: 0.921 AC: 39195 AN: 42550

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 24016 AN: 25776

East Asian (EAS) AF: 0.875 AC: 34130 AN: 39010

South Asian (SAS) AF: 0.936 AC: 78170 AN: 83540

European-Finnish (FIN) AF: 0.928 AC: 48682 AN: 52442

Middle Eastern (MID) AF: 0.914 AC: 5259 AN: 5752

European-Non Finnish (NFE) AF: 0.940 AC: 1037679 AN: 1103804

Other (OTH) AF: 0.929 AC: 55549 AN: 59794

GnomAD4 genome AF: 0.912 AC: 138724 AN: 152114 Hom.: 63388 Cov.: 30 AF XY: 0.912 AC XY: 67820 AN XY: 74360

African (AFR) AF: 0.862 AC: 35741 AN: 41480

American (AMR) AF: 0.924 AC: 14123 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3238 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4583 AN: 5132

South Asian (SAS) AF: 0.927 AC: 4466 AN: 4818

European-Finnish (FIN) AF: 0.918 AC: 9736 AN: 10602

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63817 AN: 68006

Other (OTH) AF: 0.913 AC: 1925 AN: 2108

Alfa AF: 0.927 Hom.: 96490

Bravo AF: 0.909

Asia WGS AF: 0.865 AC: 3009 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Usher syndrome type 2C (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.29
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.052
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: rs7726023; hg19: chr5-90449031;