rs13394619

chr2-11587381-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263834.9(GREB1):c.1160-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,605,816 control chromosomes in the GnomAD database, including 214,218 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (29706 hom., cov: 32)
  • Exomes 𝑓: 0.50 (184512 hom.)
• Consequence: GREB1 ENST00000263834.9 splice_acceptor
• Scores: Splicing: ADA: 0.00004143
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

Genes affected

GREB1 (HGNC:24885): (growth regulating estrogen receptor binding 1) This gene is an estrogen-responsive gene that is an early response gene in the estrogen receptor-regulated pathway. It is thought to play an important role in hormone-responsive tissues and cancer. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.889187).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREB1	NM_014668.4	c.1160-1365G>A		intron_variant		ENST00000381486.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREB1	ENST00000263834.9	c.1160-1G>A		splice_acceptor_variant		1
GREB1	ENST00000381486.7	c.1160-1365G>A		intron_variant		5	NM_014668.4	P1
GREB1	ENST00000234142.9	c.1160-1365G>A		intron_variant		1		P1
GREB1	ENST00000381483.6	c.1160-1365G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91647 AN: 151912 Hom.: 29652 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.530 AC: 131817 AN: 248880 Hom.: 36064 AF XY: 0.520 AC XY: 70046 AN XY: 134738

Gnomad AFR exome AF: 0.863

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.511

Gnomad SAS exome AF: 0.482

Gnomad FIN exome AF: 0.499

Gnomad NFE exome AF: 0.494

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.499 AC: 725024 AN: 1453786 Hom.: 184512 Cov.: 30 AF XY: 0.497 AC XY: 359556 AN XY: 723334

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.604 AC: 91765 AN: 152030 Hom.: 29706 Cov.: 32 AF XY: 0.602 AC XY: 44737 AN XY: 74302

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.590

Alfa AF: 0.514 Hom.: 39754

Bravo AF: 0.624

TwinsUK AF: 0.501 AC: 1857

ALSPAC AF: 0.479 AC: 1847

ESP6500AA AF: 0.840 AC: 3700

ESP6500EA AF: 0.499 AC: 4294

ExAC AF: 0.534 AC: 64780

Asia WGS AF: 0.520 AC: 1808 AN: 3478

EpiCase AF: 0.503

EpiControl AF: 0.505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.55
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0031	N
MutationTaster	Benign	1.0	P;P;P;P
GERP RS		-0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.010		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: rs13394619; hg19: chr2-11727507; COSMIC: COSV52183259; COSMIC: COSV52183259;