Variant 18-21383512-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001142966.3(GREB1L):c.-7G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,530,720 control chromosomes in the GnomAD database, including 29 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 (no stars).

Frequency

Genomes: 𝑓 0.0075 ( 18 hom., cov: 31)

Exomes 𝑓: 0.00069 ( 11 hom. )

Consequence

GREB1L
NM_001142966.3 splice_region

Scores

Splicing: ADA: 0.0001109

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.365

Variant links:

Genes affected

GREB1L (HGNC:31042): (GREB1 like retinoic acid receptor coactivator) Acts upstream of or within kidney development. Predicted to be integral component of membrane. Implicated in autosomal dominant nonsyndromic deafness and renal agenesis. [provided by Alliance of Genome Resources, Apr 2022]

GREB1L links:

ENSG00000265751 (HGNC:58310):

ENSG00000265751 links:

LOC101927521 (HGNC:):

LOC101927521 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 18-21383512-G-A is Benign according to our data. Variant chr18-21383512-G-A is described in ClinVar as [Benign]. Clinvar id is 3042873.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00747 (1137/152132) while in subpopulation AFR AF= 0.0264 (1094/41498). AF 95% confidence interval is 0.0251. There are 18 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1137 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1L	NM_001142966.3 link	c.-7G>A		splice_region_variant	3/33	ENST00000424526.7	NP_001136438.1
GREB1L	NM_001142966.3 link	c.-7G>A		5_prime_UTR_variant	3/33	ENST00000424526.7	NP_001136438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREB1L	ENST00000424526.7 link	c.-7G>A		splice_region_variant	3/33	5	NM_001142966.3	ENSP00000412060.1		Q9C091-1
GREB1L	ENST00000424526 link	c.-7G>A		5_prime_UTR_variant	3/33	5	NM_001142966.3	ENSP00000412060.1		Q9C091-1

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

1131

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00169

AC:

231

AN:

136594

Hom.:

AF XY:

0.00127

AC XY:

AN XY:

72272

show subpopulations

Gnomad AFR exome

AF:

0.0272

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000520

GnomAD4 exome

AF:

0.000689

AC:

950

AN:

1378588

Hom.:

Cov.:

AF XY:

0.000548

AC XY:

372

AN XY:

679350

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000373

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00747

AC:

1137

AN:

152132

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

562

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0264

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00832

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GREB1L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.4

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over