rs10895054

Variant names:

• chr11-101039579-A-T
• rs10895054
• NM_000926.4:c.2647-308T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000926.4(PGR):​c.2647-308T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,898 control chromosomes in the GnomAD database, including 1,297 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 0.11 (1297 hom., cov: 32)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 6 publications found

Genes affected

PGR (HGNC:8910): (progesterone receptor) This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.2647-308T>A		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.2155-308T>A		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1849-308T>A		intron	N/A	NP_001258090.1	P06401

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.2647-308T>A		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.2341-308T>A		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000526300.5	TSL:1	n.*122-308T>A		intron	N/A	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17420 AN: 151780 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.115 AC: 17421 AN: 151898 Hom.: 1297 Cov.: 32 AF XY: 0.112 AC XY: 8350 AN XY: 74266

African (AFR) AF: 0.0300 AC: 1243 AN: 41498

American (AMR) AF: 0.135 AC: 2061 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3462

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5188

South Asian (SAS) AF: 0.0701 AC: 338 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1576 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10784 AN: 67802

Other (OTH) AF: 0.133 AC: 281 AN: 2110

Alfa AF: 0.138 Hom.: 191

Bravo AF: 0.110

Asia WGS AF: 0.0530 AC: 186 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10895054; hg19: chr11-100910310;