rs660541

Variant names:

• chr11-101063636-G-A
• rs660541
• NM_000926.4:c.1907-884C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101063636-G-A
• chr11-101063636-G-C
• chr11-101063636-G-T

Variant summary

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

The NM_000926.4(PGR):​c.1907-884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,128 control chromosomes in the GnomAD database, including 15,705 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 0.43 (15704 hom., cov: 32)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 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.1907-884C>T		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1415-884C>T		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1415-12068C>T		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.1907-884C>T		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1907-12068C>T		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000533207.5	TSL:1	n.390C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65216 AN: 152004 Hom.: 15703 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.429 AC: 65237 AN: 152122 Hom.: 15704 Cov.: 32 AF XY: 0.439 AC XY: 32624 AN XY: 74348

African (AFR) AF: 0.209 AC: 8664 AN: 41530

American (AMR) AF: 0.496 AC: 7575 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1292 AN: 3468

East Asian (EAS) AF: 0.766 AC: 3958 AN: 5164

South Asian (SAS) AF: 0.637 AC: 3075 AN: 4824

European-Finnish (FIN) AF: 0.556 AC: 5874 AN: 10570

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33435 AN: 67974

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.473 Hom.: 31764

Bravo AF: 0.413

Asia WGS AF: 0.692 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.97
DANN	Benign	0.65
PhyloP100		-0.45
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: rs660541; hg19: chr11-100934367;