rs2117317

Variant names:

• chr18-21403805-C-T
• rs2117317
• NM_001142966.3:c.710-67C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142966.3(GREB1L):​c.710-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,324,292 control chromosomes in the GnomAD database, including 140,375 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (24545 hom., cov: 32)
  • Exomes 𝑓: 0.44 (115830 hom.)
• Consequence: GREB1L NM_001142966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• renal hypodysplasia/aplasia 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 80

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000265751 (HGNC:58310):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREB1L	NM_001142966.3	c.710-67C>T		intron_variant	Intron 6 of 32	ENST00000424526.7	NP_001136438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREB1L	ENST00000424526.7	c.710-67C>T		intron_variant	Intron 6 of 32	5	NM_001142966.3	ENSP00000412060.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82538 AN: 151918 Hom.: 24497 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.436 AC: 511240 AN: 1172256 Hom.: 115830 AF XY: 0.437 AC XY: 255578 AN XY: 584366

African (AFR) AF: 0.817 AC: 21749 AN: 26628

American (AMR) AF: 0.607 AC: 18318 AN: 30198

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 9024 AN: 22104

East Asian (EAS) AF: 0.446 AC: 15309 AN: 34288

South Asian (SAS) AF: 0.512 AC: 36479 AN: 71246

European-Finnish (FIN) AF: 0.447 AC: 20778 AN: 46518

Middle Eastern (MID) AF: 0.534 AC: 2739 AN: 5134

European-Non Finnish (NFE) AF: 0.410 AC: 363601 AN: 886322

Other (OTH) AF: 0.467 AC: 23243 AN: 49818

GnomAD4 genome AF: 0.544 AC: 82648 AN: 152036 Hom.: 24545 Cov.: 32 AF XY: 0.545 AC XY: 40520 AN XY: 74312

African (AFR) AF: 0.796 AC: 33056 AN: 41506

American (AMR) AF: 0.562 AC: 8588 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2351 AN: 5154

South Asian (SAS) AF: 0.525 AC: 2531 AN: 4820

European-Finnish (FIN) AF: 0.436 AC: 4603 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28594 AN: 67938

Other (OTH) AF: 0.527 AC: 1112 AN: 2110

Alfa AF: 0.483 Hom.: 9345

Bravo AF: 0.562

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.60
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs2117317; hg19: chr18-18983766; COSMIC: COSV52550906;