17-9901082-T-C

Position:

• chr17-9901082-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002903.3(RCVRN):​c.400A>G​(p.Thr134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,600,624 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (13 hom.)
• Consequence: RCVRN NM_002903.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.663

Genes affected

RCVRN (HGNC:9937): (recoverin) This gene encodes a member of the recoverin family of neuronal calcium sensors. The encoded protein contains three calcium-binding EF-hand domains and may prolong the termination of the phototransduction cascade in the retina by blocking the phosphorylation of photo-activated rhodopsin. Recoverin may be the antigen responsible for cancer-associated retinopathy. [provided by RefSeq, Jul 2008]

RCVRN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025858283).
• BP6: Variant 17-9901082-T-C is Benign according to our data. Variant chr17-9901082-T-C is described in ClinVar as [Benign]. Clinvar id is 781346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1114/152034) while in subpopulation AFR AF= 0.0256 (1061/41450). AF 95% confidence interval is 0.0243. There are 19 homozygotes in gnomad4. There are 510 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCVRN	NM_002903.3	c.400A>G	p.Thr134Ala	missense_variant	2/3	ENST00000226193.6	NP_002894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCVRN	ENST00000226193.6	c.400A>G	p.Thr134Ala	missense_variant	2/3	1	NM_002903.3	ENSP00000226193.5
RCVRN	ENST00000570909.3	n.121A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1111 AN: 151916 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00205 AC: 504 AN: 245432 Hom.: 8 AF XY: 0.00160 AC XY: 213 AN XY: 132748

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000684

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000892

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.000696 AC: 1008 AN: 1448590 Hom.: 13 Cov.: 28 AF XY: 0.000597 AC XY: 429 AN XY: 718964

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000704

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000281

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00733 AC: 1114 AN: 152034 Hom.: 19 Cov.: 32 AF XY: 0.00686 AC XY: 510 AN XY: 74290

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00139 Hom.: 1

Bravo AF: 0.00811

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0247 AC: 109

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00246 AC: 299

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.11
Sift	Benign	0.060	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.082
MVP		0.59
MPC		0.34
ClinPred		0.00078	T
GERP RS		2.3
Varity_R		0.13
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7216623; hg19: chr17-9804399;