chr14-21310558-AAAT-A

Variant names:

• chr14-21310558-AAAT-A
• rs398099213
• NM_020366.4:c.907-16_907-14delAAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020366.4(RPGRIP1):​c.907-16_907-14delAAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,225,388 control chromosomes in the GnomAD database, including 33,568 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4068 hom., cov: 26)
  • Exomes 𝑓: 0.23 (29500 hom.)
• Consequence: RPGRIP1 NM_020366.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.20
• Publications: 1 publications found

Genes affected

RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

RPGRIP1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 13

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Leber congenital amaurosis 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-21310558-AAAT-A is Benign according to our data. Variant chr14-21310558-AAAT-A is described in ClinVar as Benign. ClinVar VariationId is 198579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1	NM_020366.4	c.907-16_907-14delAAT		intron_variant	Intron 7 of 24	ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7	c.907-25_907-23delAAT		intron_variant	Intron 7 of 24	1	NM_020366.4	ENSP00000382895.2
RPGRIP1	ENST00000557771.5	c.826-25_826-23delAAT		intron_variant	Intron 6 of 23	5		ENSP00000451219.1
RPGRIP1	ENST00000556336.5	c.826-25_826-23delAAT		intron_variant	Intron 6 of 20	5		ENSP00000450445.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33656 AN: 151806 Hom.: 4062 Cov.: 26

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.254 AC: 32394 AN: 127760 AF XY: 0.255

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.308

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.226 AC: 242543 AN: 1073464 Hom.: 29500 AF XY: 0.229 AC XY: 124155 AN XY: 542496

African (AFR) AF: 0.114 AC: 2635 AN: 23166

American (AMR) AF: 0.359 AC: 7107 AN: 19824

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 4257 AN: 21502

East Asian (EAS) AF: 0.280 AC: 9238 AN: 32998

South Asian (SAS) AF: 0.286 AC: 17485 AN: 61098

European-Finnish (FIN) AF: 0.231 AC: 11291 AN: 48816

Middle Eastern (MID) AF: 0.240 AC: 1199 AN: 4992

European-Non Finnish (NFE) AF: 0.220 AC: 179093 AN: 814558

Other (OTH) AF: 0.220 AC: 10238 AN: 46510

GnomAD4 genome AF: 0.222 AC: 33675 AN: 151924 Hom.: 4068 Cov.: 26 AF XY: 0.226 AC XY: 16783 AN XY: 74238

African (AFR) AF: 0.130 AC: 5383 AN: 41478

American (AMR) AF: 0.333 AC: 5068 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1552 AN: 5158

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2356 AN: 10534

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16420 AN: 67948

Other (OTH) AF: 0.226 AC: 475 AN: 2098

Alfa AF: 0.230 Hom.: 826

Bravo AF: 0.225

Asia WGS AF: 0.307 AC: 1064 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 01, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 18055820) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs398099213; hg19: chr14-21778717;