rs2117317

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000265751 (HGNC:58310):

LOC101927521 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.817

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.467

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

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.527

Alfa AF: 0.473 Hom.: 5889

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

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