NM_000926.4:c.1907-831C>G

Variant names:

• chr11-101063583-G-C
• rs660149
• NM_000926.4:c.1907-831C>G

Variant summary

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

The NM_000926.4(PGR):​c.1907-831C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,128 control chromosomes in the GnomAD database, including 42,717 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 0.75 (42713 hom., cov: 32)
  • Exomes 𝑓: 0.58 (4 hom.)
• Consequence: PGR NM_000926.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.1907-831C>G		intron	N/A	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1415-831C>G		intron	N/A	NP_001189403.1	P06401-2
	PGR	NM_001271161.2		c.1415-12015C>G		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.1907-831C>G		intron	N/A	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1907-12015C>G		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000533207.5	TSL:1	n.443C>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113572 AN: 151984 Hom.: 42658 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.577 AC: 15 AN: 26 Hom.: 4 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.545 AC: 12 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.747 AC: 113683 AN: 152102 Hom.: 42713 Cov.: 32 AF XY: 0.751 AC XY: 55837 AN XY: 74338

African (AFR) AF: 0.717 AC: 29748 AN: 41490

American (AMR) AF: 0.794 AC: 12133 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2668 AN: 3470

East Asian (EAS) AF: 0.989 AC: 5110 AN: 5166

South Asian (SAS) AF: 0.767 AC: 3700 AN: 4822

European-Finnish (FIN) AF: 0.780 AC: 8247 AN: 10576

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49719 AN: 67992

Other (OTH) AF: 0.752 AC: 1588 AN: 2112

Alfa AF: 0.743 Hom.: 5198

Bravo AF: 0.747

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		-0.081
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: rs660149; hg19: chr11-100934314;