2-11580774-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014668.4(GREB1):c.843G>A(p.Pro281=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,614,142 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (92 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (93 hom.)
• Consequence: GREB1 NM_014668.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-11580774-G-A is Benign according to our data. Variant chr2-11580774-G-A is described in ClinVar as [Benign]. Clinvar id is 780337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREB1	NM_014668.4	c.843G>A	p.Pro281=	synonymous_variant	7/33	ENST00000381486.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREB1	ENST00000381486.7	c.843G>A	p.Pro281=	synonymous_variant	7/33	5	NM_014668.4	P1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3036 AN: 152172 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00502 AC: 1261 AN: 251426 Hom.: 35 AF XY: 0.00383 AC XY: 521 AN XY: 135892

Gnomad AFR exome AF: 0.0658

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00219 AC: 3200 AN: 1461852 Hom.: 93 Cov.: 31 AF XY: 0.00187 AC XY: 1358 AN XY: 727228

Gnomad4 AFR exome AF: 0.0724

Gnomad4 AMR exome AF: 0.00423

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.0200 AC: 3050 AN: 152290 Hom.: 92 Cov.: 33 AF XY: 0.0194 AC XY: 1445 AN XY: 74466

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00675 Hom.: 26

Bravo AF: 0.0226

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	8.6
Dann	Benign	0.88

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: rs16857665; hg19: chr2-11720900;