rs4669749

Positions:

• chr2-11552538-C-A
• chr2-11552538-C-G
• chr2-11552538-C-T

Variant summary

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

The NM_014668.4(GREB1):​c.-161-3916C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,078 control chromosomes in the GnomAD database, including 38,602 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 0.71 (38602 hom., cov: 32)
• Consequence: GREB1 NM_014668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4	c.-161-3916C>A		intron_variant		ENST00000381486.7	NP_055483.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREB1	ENST00000381486.7	c.-161-3916C>A		intron_variant		5	NM_014668.4	ENSP00000370896	P1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107993 AN: 151960 Hom.: 38575 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.675

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.711 AC: 108081 AN: 152078 Hom.: 38602 Cov.: 32 AF XY: 0.717 AC XY: 53309 AN XY: 74322

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.675

Alfa AF: 0.691 Hom.: 74000

Bravo AF: 0.706

Asia WGS AF: 0.824 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.021
DANN	Benign	0.54

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: rs4669749; hg19: chr2-11692664;