2-11621183-T-C

Position:

• chr2-11621183-T-C

Variant summary

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

The NM_014668.4(GREB1):​c.4147+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,256 control chromosomes in the GnomAD database, including 66,916 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 0.94 (66916 hom., cov: 33)
• Consequence: GREB1 NM_014668.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREB1	NM_014668.4	c.4147+176T>C		intron_variant		ENST00000381486.7	NP_055483.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREB1	ENST00000381486.7	c.4147+176T>C		intron_variant		5	NM_014668.4	ENSP00000370896	P1
GREB1	ENST00000234142.9	c.4147+176T>C		intron_variant		1		ENSP00000234142	P1
GREB1	ENST00000396123.2	c.1141+176T>C		intron_variant		1		ENSP00000379429

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142480 AN: 152138 Hom.: 66847 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.937 AC: 142610 AN: 152256 Hom.: 66916 Cov.: 33 AF XY: 0.936 AC XY: 69674 AN XY: 74454

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.925

Alfa AF: 0.936 Hom.: 30085

Bravo AF: 0.937

Asia WGS AF: 0.851 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.74

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: rs2304401; hg19: chr2-11761309;